W > DO
u< OU_1 64568 >m
^ OQ X CO
OSMANIA UNIVERSITY LIBRARY
Cal, No.
No .
Author
This booUld be returned on|? r before the date last marked beJ
ORGANIC SYNTHESES
THESE VOLUMES NOW READY
Volume I.
ROGER ADAMS, University of Illinois, Editor-in-
Chief. vi+84 pages, 6 by 9; 7 figures Cloth.
Volume II.
JAMES BRYANT CONANT, Harvard University,
Editor-in-Chief, vii-f 100 pages, 6 by 9; 3 figures.
Cloth.
Volume III.
HANS THACHER CLARKE, Columbia University,
Editor-m-Chief. 4+105 pages, 6 by 9; 3 f.gures.
Cloth.
Volume IV.
OLIVER KAMM, Parke, Davis, and Company, Editor-
in-Chief, v-f 89 pages, 6 by 9; 3 figures. Cloth.
Volume V.
CARL SHIPP MARVEL, University of Illinois, Editor-
in-Chief 4+ 1 10 pages, 6 by 9; 3 figures. Cloth.
Volume VI.
HENRY OILMAN, Iowa State College, Editor-in-
Chief v+i2o pages; 6 by 9; 5 figures. Cloth.
Volume VII.
FRANK C. WHITMORE, Northwestern University,
Editor-in-Chief, vii-f- 105 pages; 6 by 9; i figure.
Cloth.
Volume VIII.
ROGER ADAMS, University of Illinois, Editor-in-
Chief, v-f 139 pages; 6 by 9; 3 figures. Cloth.
Volume IX.
JAMES BEY ANT CONANT, Harvard jUniversity,
Editor-in-Chief, vii-f 108 pages, 6 by 9; i figure.
Cloth.
Volume X
HVNS THACHER CLARKE, Columbia University,
Editor-in-Chief, vii-f 115 pages, 6 by 9; 4 figures.
Cloth.
ORGANIC SYNTHESES
AN ANNUAL PUBLICATION OF SATISFACTORY
METHODS FOR THE PREPARATION
OF ORGANIC CHEMICALS
EDITORIAL BOARD
OLIVER KAMM, Editor-in-Chief
ROGER ADAMS J. B. CONANT
H. T. CLARKE C. S. MARVEL
F. C. WHITMORE
W. G. CHRISTIANSEN
A. W. Dox
GRAHAM EDGAR
L. F. FIESER
HENRY GILMAN
CONTRIBUTORS
J. W. HOWARD
C. D. KURD
S. M. McELVAIN
J. F. NORRIS
J. A. NlEUWLAND
C. S. PALMER
PICATINNY ARSENAL
J. S. REICHERT
F. K. THAYER
E. B. VLIET
VOL. IV.
NEW YORK
JOHN WILEY & SONS, INC.
LONDON: CHAPMAN & HALL, LIMITED
Copyright, 1925
BY
ROGER ADAMS
All Rights Reserved
This book or any part thereof must not
be reproduced in any form mthout
the written permission of the publisher.
Printed in U. S. A.
PRESS OF
SRAUNWORTH ft CO.. INC.
BROOKLYN, NEW YORK
PREFACE TO VOLUME IV
THE general plan outlined in the first volume of the series
has been followed in the subsequent publications; but it has
been found advisable to include preparations which are carried
out on a somewhat reduced scale, since the carefully described
directions have found application not merely in the semi-
commercial preparation of needed research chemicals and
reagents but also in the instruction of graduate students enter-
ing the organic field. However, it is the experience of the
editors that the reduction of preparations described on a large
scale is usually less difficult than the reverse procedure.
The sections on " Other Methods of Preparation" are not
intended to include all possible methods but rather those that
are of interest chiefly from the preparative standpoint. The
Cumulative Index, started with Volume III, is being continued.
The friendly cooperation of other workers in Organic Chem-
istry has been gratifying, and the editors again cordially invite
contributions from any investigator who has occasion to study
an organic preparation exhaustively enough to justify the
presentation of certified directions.
ORGANIC SYNTHESES
ACETYL MANDELYL CHLORIDE
C 6 H 5 CHOHCO 2 H-f CHaCOCl ->
C 6 H 5 CH(OCOCH3)CO2H-fHCl
C 6 H 5 CH(OCOCH3)C02H+SOCl2 ->
C 6 H 5 CH(OCOCH3)COC1+SO 2 +HC1
Prepared by F. K. THAYER.
Checked by ROGER ADAMS and E. E. DREGER.
1. Procedure
IN a 500-cc. Claisen distilling flask with a low side-tube
connected to a condenser, are placed 105 g. of mandelic acid
(m.p. 118) and 151 g. of acetyl chloride. A reaction sets in
without the application of heat (Note i). As soon as a clear
solution results, the flask is warmed on a water bath and the
excess acetyl chloride is distilled. The last trace of acetyl
chloride may be removed by prolonged drying in a vacuum.
The acetyl mandelic acid then crystallizes in large, round,
white clusters after one or two days' standing. The yield is
130-133 g. (97-99 per cent of the theoretical amount) (Note 2).
To the crude acetyl mandelic acid still containing some
acetyl chloride obtained as described above, is added 250 g. of
thionyl chloride. The reaction starts at once without warming
but it is necessary to reflux for four hours to complete the
reaction (Note 3). The excess thionyl chloride is then distilled
2 ORGANIC SYNTHESES
and the residue distilled in a vacuum (Note 4). The yield is
115-120 g. (79-83 per cent of the theoretical amount) of almost
colorless liquid boiling at i25-i30/io mm. (i5o-i55/33 mm.).
2. Notes
1. Occasionally the application of a little heat is necessary
to bring about a more rapid acetylation.
2. The melting points given in the literature range from
39 to 80. The acetyl mandelic acid is difficult to crystallize
but may be purified from benzene or chloroform, preferably
the former. The product thus obtained melts at about 79-80.
3. Prolonged refluxing of the acetylated mandelic acid with
the thionyl chloride tends to lower the yield.
4. Anschiitz gives the boiling point of acetyl mandelyl
chloride as 129 '/io mm. The vacuum used should be as low
as possible, to avoid the formation of tar during the distillation.
3. Other Methods of Preparation
Acetyl mandelic acid was described by Naquet and Lougui-
nine, 1 but their product has been shown to be contaminated
with the ethyl ester of acetyl mandelic acid. Dupont 2 obtained
the compound by the oxidation of diacetyl i, 4-diphenylbutine-
2-diol-i, 4. Anschiitz and Bocker 3 prepared acetyl mandelic
acid, and from it the acid chloride, by the use of phosphorus
pentachloride, but with poor yields. Von Braun and Mliller 4
state that acetyl mandelyl chloride can be made from acetylated
mandelic acid and thionyl chloride, the resulting product being
a viscous yellow oil.
1 Compt. rend. 62, 430 (1866); Ann. 139, 302 (1866).
2 Compt. rend. 150, 1525 (1910).
3 Ann. 368, 57, 59 (1909).
4 Ber. 51, 244 (1918).
II
a-AMINO-n-CAPROIC ACID
CH3(CH2J3CHNH2CO 2 H+NH 4 Br
Prepared by C. S. MARVEL and V. DU VIGNEAUD.
Checked by H T. CLARKE and E. R. TAYLOR.
1. Procedure
IN a i-l. round-bottom flask is placed 760 g. of concentrated
ammonium hydroxide (sp. gr. 0.9) and to this is slowly added
150 g. of a-bromocaproic acid (Note i). The flask is well
stoppered and allowed to stand in a warm place (50-55) for
twenty to thirty hours. The amino acid separates and is fil-
tered off with suction and washed with methyl alcohol (Note 2) .
This crop of crystals weighs 51-56 g. The aqueous filtrate is
evaporated nearly to dryness on a steam bath and then treated
with about 250 cc. of methyl alcohol. This precipitates a sec-
ond crop of amino acid contaminated with ammonium bromide.
On washing with methyl alcohol and recrystallizing from water,
there is obtained 10-15 g- niore of pure product. The total
yield is 63-68 g, (62-67 per cent of the theoretical amount).
2. Notes
1. The once-distilled bromocaproic acid (p. 9) is satisfac-
tory.
2. If the amino acid is not carefully washed with alcohol, it
contains ammonium bromide and may possess an objectionable
3
ORGANIC SYNTHESES
odor. Methyl alcohol is preferable to ethyl alcohol since it dis-
solves ammonium bromide more readily.
3. Other Methods of Preparation
a-Amino-w-caproic acid has been prepared by the action of
ammonia on a-bromo-rc-caproic acid. 1
1 J. prakt. Chem (2) 1, 7 (1870); Ber. 33, 2381 (1900); Z. physiol. Chem. 86,
456 (1913); J. Am. Chem. Soc. 42, 320 (1920).
Ill
ARSONO- AND ARSENOACETIC ACIDS
ClCH 2 C0 2 Na+Na 3 As03 -> NaCl + CH 2 (CO 2 Na)AsO3Na 2
2CH 2 (CO 2 H)As03H 2 +8H(H 3 PO 2 ) - AsCH 2 CO 2 H+6H 2 O
I!
AsCHoCOoH
Prepared by C. S. PALMER.
Checked by OLIVER KAMM.
1. Procedure
ONE HUNDRED grams of powdered arsenious oxide is added to
the hot solution obtained by dissolving 160 g. of sodium hydrox-
ide in 300 cc. of water. After the solution has cooled to 20,
48 g. of chloroacetic acid is added. The suspension is well
stirred during about five minutes, when a strongly exothermic
reaction begins, the temperature rises to 70-75, and a clear
solution results.
The reaction mixture is permitted to stand at room tempera-
ture during one hour, or longer if desired (Note i). The solu-
tion is acidified with 160 cc. of glacial acetic acid and, after the
temperature has been lowered to 40 by cooling, the precipi-
tated arsenious oxide is filtered off by suction and washed with
50 cc. of water.
The filtrate is poured into a solution containing 185 g. of
crystallized barium chloride dissolved in 600 cc. of hot water.
Barium arsonoacetate, Ba(O 2 CCH 2 AsOaBa) 2 (hydrated), forms
a thick, finely divided precipitate. The mixture is stirred for
several minutes and then allowed to stand until the following
day, when it is filtered upon a is-cm. Biichner funnel and washed
5
6 ORGANIC SYNTHESES
thoroughly with water (Note 2). The yield of air-dry * product
is 220 g. (96 per cent of the theoretical amount).
Sodium arsonoacetate is prepared by adding the freshly
filtered and washed barium arsonoacetate as obtained above
(without drying) to a solution of 108 g. of anhydrous sodium
sulfate in 500 cc. of hot water. The mixture is mechanically
stirred for one hour, the barium sulfate filtered off, and the
filtrate concentrated on the steam bath until crystallization
commences. Upon cooling and stirring (Note 3), sodium arsono-
acetate separates and is filtered by suction, the filtrate being
concentrated to obtain a second crop of crystals. The yield of
the combined fractions is 100-110 g. (80-88 per cent of the
theoretical amount).
A solution of 12.5 g. of sodium arsonoacetate and 30 g. of
sodium hypophosphite (NaH 2 PO2-HoO) in 150 cc. of cold 15
per cent sulfuric acid is allowed to stand at room temperature.
After two or three days, the yellow precipitate is filtered off,
washed with water, and dried in a vacuum over sulfuric acid or
phosphorus pentoxide. A second crop is obtained by allowing
the mother liquid to stand for two days longer.
The arsenoacetic acid consists of minute yellow needles,
which do not melt below 260 although they undergo consider-
able decomposition above 200. The yield is 5 g. (74 per cent
of the theoretical amount).
2. Notes
i. The reaction between sodium arsenite and chloroacetic
acid is very rapid, as may easily be demonstrated by titrating
i-cc. portions of the solution with N/io iodine, according to the
usual volumetric method for arsenious acid, before and after
the reaction with chloroacetic acid. The excess of sodium
arsenite is necessary, as was learned by means of an iodometric
study of the reaction.
* The air-dry sample contains 13 per cent of water of hydra tion, as deter-
mined by actual analysis.
ARSONO- AND ARSENOACETIC ACIDS 7
2. If the thick paste is not allowed to stand over night,
filtration is more cumbersome and it is extremely difficult to
wash the precipitate free from arsenites. With this precaution,
it is found that after five washings with 25<D-cc. portions of water,
the final filtrate, as well as the desired barium salt, is practically
free from iodine-reducing compounds.
3. Stirring is required during the crystallization process,
since otherwise the product tends to form a solid cake. The
sodium salt is obtained without water of crystallization.
Usually, it contains a trace of sulfate but this does not interfere
with its subsequent use. The sulfate may be removed by
recrystallization from water.
3. Other Methods of Preparation
Arsonoacetic acid was obtained by Ehrlich and Bertheim l
by treating /?-aminophenylarsenoacetic acid with bromine. It
has been prepared by the action of three molecular equivalents
of sodium chloroacetate on two of sodium arsenite, followed by
isolation as the calcium salt, 2 but it is found that these pro-
portions are less satisfactory than the ones adopted. 3 Arseno-
acetic acid has been prepared recently by Palmer. 3
1 Ber. 43, 926 (1910).
2 U. S. Pat. 1,445,685; Austrian Pat. 93,325; Swiss Pat. 97,977.
3 J. Am. Chem. Soc. 45, 3023 (1923).
IV
a-BROMO-n-CAPROIC ACID
CH8(CH 2 )4C0 2 H+Br2(PCl 3 ) -> CH 3 (CH.,) 3 CHBrCO 2 H+HBr
Prepared by II. T. CLARKE and E. R. TAYLOR.
Checked by C. S. MARVEL and R. L. SIIRINER.
1. Procedure
Two HUNDRED grams of freshly distilled dry w-caproic acid
is placed in a i-l. flask with 300 g. of bromine which has been
dried by washing once with 200 cc. of concentrated sulfuric
acid (Note i). A j-cc. portion of phosphorus trichloride is
cautiously added and the flask connected to a reflux condenser
(Note 2), the top of which is connected with a trap and absorp-
tion bottle containing water. The mixture is then heated in a
water or oil bath to 65-70, at which temperature the reaction
commences and hydrobromic acid is given off smoothly. After
five to six hours, the bromine has all reacted (Note 3). Towards
the end of the reaction, the temperature is allowed to rise to
about 100. The contents of the flask are now distilled under
diminished pressure (Note 4). The fraction boiling at 132-
I40/i5 mm. is collected and amounts to 280-298 g. (81-80
per cent of the theoretical amount).
2, Notes
1. The reagents must be dry or the yield will be lowered.
2. A flask fitted with a ground -glass connection to the reflux
condenser will assist in reducing the amount of tar.
3. For larger runs, a longer time is required. A run of 2 kg.
of caproic acid requires about fifteen hours.
9
10 ORGANIC SYNTHESES
4. It is best to distil the first low-boiling fractions with a
water pump, since a considerable amount of hydrogen bromide
is evolved. In order to obtain a light-colored product, the dis-
tillation should take place under as low pressure as possible.
The a-bromo-ft-caproic acid boils at n6-i25/S mm. The
product obtained is sufficiently pure for most purposes; upon
redistillation, however, it comes over almost entirely between
i28-i3i/io mm.
3. Other Methods of Preparation
a-Bromo-w-caproic acid has been prepared by heating
n-caproic acid with bromine in a sealed tube to 140 l and with
bromine and phosphorus; 2 also by the action of heat on
a-bromobutylmalonic acid. 3
*Z. Chem. 1868, 616; J. prakt. Chem. (2) 1, 7 (1870).
2 Ber. 24, 2222 (1891); 33, 2381 (1900); Z. physiol. Chem. 86, 455 (1913).
8 J. Am. Chem. Soc. 42, 319 (1920).
V
n-BUTYLMALONIC ESTER (ETHYL)
Prepared by ROGER ADAMS and R. M. KAMM.
Checked by F. C. WHITMORE and MILTON PUTERBAUGH.
1. Procedure
A 5-!. round-bottom flask, fitted with a rubber stopper
holding a reflux condenser, a separatory funnel, and a mechani-
cal stirrer, is clamped over a steam or water bath. In the flask
is placed 2.5 1. of absolute alcohol (Note i) and then there is
added gradually, through the condenser, 115 g. of clean sodium
cut into pieces of suitable size. If the action becomes too
violent, the mixture may be cooled by water poured over the
outside of the flask. The sodium alcoholate solution is stirred,
and cooled to about 50, after which 825 g. (780 cc.) of diethyl
malonate (Note 2) is added slowly through the separatory
funnel. To the clear solution is added gradually 685 g. (545 cc.)
of w-butyl bromide (Note 3). The reaction commences almost
immediately and considerable heat is generated. If the addi-
tion is too rapid, the reaction may become violent enough to
require cooling of the flask by pouring water over it. Up to
this point, the time required is about two hours.
The reaction mixture is refluxed until neutral to moist
litmus; this requires about two hours. The flask is then con-
nected with a condenser set for distillation. As much alcohol
as possible is distilled off by means of the steam or water bath.
12 ORGANIC SYNTHESES
A period of about six hours is required for this distillation and
about 2 1. of alcohol is recovered.
The residue from which no more alcohol can be distilled is
treated with about 2 1. of water and shaken thoroughly. The
upper layer of ;z-butylmalonic ester is separated (Note 4) and
distilled under diminished pressure from a 2- or a 3-!. Claisen
flask. First a low-boiling portion is collected, consisting
of alcohol, water, and butyl bromide; then a small inter-
mediate fraction of unchanged malonic ester comes over;
and finally w-butylmalonic ester boiling at i4o-i45/4 mm.,
I30-i35/ 20 nim., and 235-24o/76o mm . The first fractions
amount to less than 100 cc., while the main fraction amounts to
860-970 g. (80-90 per cent of the theoretical amount).
2. Notes
1. The quality of the absolute alcohol used has a very
marked effect upon the yield. It is a wise procedure to reflux
ordinary " absolute " alcohol with about one- twentieth of its
weight of sodium and then to distil it directly into the flask in
which it is to be used.
A trial run with alcohol of 98.4 per cent purity gave only a
66 per cent yield.
2. The malonic ester used should be redistilled, preferably
under diminished pressure, and a 2-degree fraction used in the
preparation. Ordinary commercial malonic ester contains up
to 15 per cent of low-boiling impurities.
3. Redistilled w-butyl bromide boiling over a i -degree range
should be used.
4. It is not practical to filter off the sodium bromide either
before or after the distillation of the alcohol, as the separation
of the ester from the water layer is then very difficult.
3. Other Methods of Preparation
H-Butylmalonic ester has been prepared only by the action
of n- butyl halides on sodium malonic ester. 1
1 Ber. 28, 2622 (1895); J. Am. Chem. Soc. 42, 316 (1920).
VI
o-CHLOROMERCURIPHENOL
C 6 H 5 OH+Hg(OCOCH3) 2 ->
HOC 6 H 4 HgOCOCH 3 +NaCl -> CH 3 C0 2 Na+HOCoII 4 HgCl
Prepared by F. C. WHITMORE and E R. HANSON.
Checked by J. H. C'ONANT and R. M. GRANARA.
1. Procedure
Two liters of water is heated to boiling in a 3-!. flask. Mean-
while 50 g. of phenol, in a 250-00. tall beaker provided with a
small glass mechanical stirrer, is heated to 170 on an electric
heater (Note i). The heat is then turned off and TOO g. of
powdered mercuric acetate is added gradually (five to ten
minutes) to the stirred phenol. After all of the mercuric ace-
tate has dissolved in the phenol, the mercuration mixture is
poured slowly into the hot water, the burner having previously
been removed (Note 2). The beaker is rinsed out with some of
the hot water. The mixture is boiled for five minutes and then
filtered through filter paper in a large Buchner funnel which has
been previously heated by blowing steam through it. The
pink residue (Note 3) consists of a small amount of dimercurated
phenol and some polymerization products.
The filtrate is again brought to boiling in a clean flask and
treated with a solution of 20 g. of sodium chloride in 200 cc. of
boiling water. The precipitate formed is ^-chloromercuri-
phenol together with some colored impurities (Note 4). The
mixture is heated to boiling and filtered through a large pre-
heated Buchner funnel. The filtrate on cooling deposits white
feathery crystals of 0-chloromercuriphenol. The mixture is
13
14 ORGANIC SYNTHESES
*
allowed to stand at least twelve hours and then filtered. The
crystals are air-dried. They should be colorless and should
melt above 147 (m.p. of pure substance 152). If the product
is pink or melts low it should be recrystallized from hot water.
The average yield of fifteen experiments was 45 g. of ortho
compound melting above 147, which corresponds to 44 per cent
of the theoretical amount.
2. Notes
1. Mercuration at lower temperatures than that recom-
mended gives a poorer yield of the ortho compound.
2. If the heat is not removed from under the water before
the mercuratecl phenol is added, the mixture is likely to froth
over.
3. Long heating of the mercuration mixture increases the
amount of pink by-product.
4. The yield of impure para compound obtained as a by-
product varies from 10 to 30 g.
5. A saturated solution of bromine in glycerol should be
kept at hand as an antidote for phenol burns. If all undis-
solved bromine is allowed to settle out before the solution is
used, there is no danger of bromine burns.
3. Other Methods of Preparation
Phenol has been mercurated in water solution 1 and without
the use of any solvent but the phenol itself. 2
1 Ber. 35, 2855 (1902).
2 J. Am. Chem. Soc. 43, 622 (1921).
VII
CREATININE
NH=C(NH 2 )N(CH3)CH 2 CO2H -
/NH CO
NH=C( | +H 2 O
\N(CH 3 ) CH 2
Prepared by GRAHAM EDGAR and W S. HINEGARDNER.
Checked by II. T. CLARKE and Ross PHILLIPS.
1. Procedure
A. Creatinine. A mixture of 900 g. of commercial creatine
hydrate (Note i) with 550 cc. of concentrated hydrochloric
acid (sp. gr. 1.19) and 150 cc. of water is warmed in a 3-!. flask
on the steam bath for twenty-four hours. The hot solution is
filtered and chilled to 0-5 in an ice bath, and to it is added
1000 cc. of 28 per cent aqueous ammonia (sp. gr. 0.90). The
flask is immersed in an ice-salt bath and the mixture is stirred
vigorously until the temperature falls to o, when the crystal-
line creatinine is filtered off, washed with ice-cold 28 per cent
aqueous ammonia (Note 2) until the filtrate is free of chlorides,
and finally with ice-cold methyl alcohol; the product (Note 3)
is then dried to constant weight at 40-50. The yield (Note 4)
is 545-555 g. (80-8 1 per cent of the theoretical amount).
B. Creatinine Zinc Chloride. An intimate mixture of 400 g.
of commercial creatine hydrate and 400 g. of fused zinc chloride
is heated in a porcelain dish over a small flame. The mixture
melts to a viscous liquid which soon solidifies. The flame is
removed when the mixture can no longer be stirred. The mass,
when cold, is broken up, and stirred with 500 cc. of cold water
until the lumps are softened; the crude creatinine zinc chloride
is filtered off with suction, by the use of a hardened filter paper,
15
16 ORGANIC SYNTHESES
and washed with ice water to remove excess zinc chloride. The
crude material is now dissolved in 6 1. of boiling 25 per cent
aqueous acetic acid, filtered with the use of a little decolorizing
carbon, and the solution allowed to stand for forty-eight hours.
The crystals that have separated are filtered off, washed with
ice water, and dried. Weight 220-230 g. The filtrate and
washings are evaporated to 4.5 1. under reduced pressure in a
12-1. flask; 6.5 1. of methyl alcohol is added and the mixture
allowed to stand in a cool place for twenty-four hours. The
crystals that separate are filtered off, washed with cold water
and dried, and an additional 150-160 g. is thus obtained. The
total yield is 370-380 g. (76-78 per cent of the theoretical
amount) .
C. Creatinine Picrate. A mixture of 300 g. of commercial
creatine hydrate with 190 cc. of concentrated hydrochloric acid
(sp. gr. 1.19) and 50 cc. of water is warmed in a glass or porce-
lain dish on a steam bath for twenty-four hours. The resulting
mass of creatinine hydrochloride crystals is dissolved in i 1. of
water, boiled with a little decolorizing carbon, and filtered.
The solution is then diluted to 4 1. with distilled water, and
heated to boiling in a 12-!. flask under a reflux condenser. To
the hot solution is added, with good stirring, a solution of 500 g.
of technical picric acid (containing 10 per cent of water) in
1250 cc. of warm methyl alcohol. Stirring is continued for one
hour on the steam bath and the solution allowed to cool. The
crystalline precipitate of creatinine picrate is filtered off, washed
well with cold water, and dried. It forms long needles which
melt at 220; the melting point (Note 5) is unchanged on recrys-
tallization from hot water. The yield is 620-630 g. (89-90 per
cent of the theoretical amount) .
2. Notes
i. As a rule, the commercial product, which contains one
mol of water of crystallization, is entirely satisfactory; but if it
is dark in color, it may be recrystallized from water with the
use of decolorizing carbon.
CREATININE 17
2. Creatinine dissolves readily in pure water but is only
slightly soluble in cold concentrated ammonia, while ammonium
chloride is freely soluble.
3. The creatinine so prepared is practically 100 per cent
pure; its recrystallization, while not recommended, may be
carried out by dissolving, as rapidly as possible, i part by weight
in 5 parts of water previously warmed to 65, and then immedi-
ately adding to the warm solution double its volume of acetone,
chilling in ice, and filtering after a few hours. The product is
finally washed with acetone and dried. About one-third is lost
in the nitrate.
4. The yield could be slightly increased by so modifying the
conditions that the total volume of filtrate would be smaller,
but this would involve an undue amount of trouble.
5. Special attention was given to the melting point deter-
mination, since two values, 205 and 212-213, have been
recorded in the literature.
3. Other Methods of Preparation
Creatinine has been prepared generally from urine ] or
muscle, 2 though its formation from creatine by the action of
mineral acids has also been studied. 3 The conversion of crea-
tine into creatinine has also been effected by heating in an
autoclave * and by treatment with zinc chloride/ 5 The above
technique has been developed rt since creatine has become avail-
able in relatively large quantities as a by-product. 7
1 Ann. 119, 39 (1861); 159, 279 (1871).
2 Gazz. chim. ital. 17, 382 (1887).
3 Ann. f>2, 298 (1847); J Am. Chem. Soc. 45, 2242 (1923).
4 J. Biol. Chem. 8, 399 (1910).
6 Jahresb. 1857, 544; J. Biol. Chem. 18, 183 (1914).
6 J. Biol. Chem. 50, 3, 88 1 (1923).
7 J. Ind. Eng. Chem. 14, 984 (1922).
VIII
CUPFERRON
C G H5NHOH+C4H 9 ONO+NH3 -
C H 5 N(NO)ONH4+C4H 9 OH
Prepared by C S. MARVEL.
Checked by OLIVER KAMM.
1. Procedure
THE moist phenylhydroxylamine obtained from 1000 g. of
nitrobenzene, by the method described on page 57, is weighed
and dissolved in 4.5 1. of ordinary ether (Note i). The ether-
insoluble material (sodium chloride and water) is also weighed,
the difference between the two weighings being a fairly accurate
measure of the amount of phenylhydroxylamine in solution.
The ether solution is filtered through a dry filter paper into a
5-1. round-bottom flask which is fitted with an efficient mechani-
cal stirrer and immersed in an ice-salt bath. When the tempera-
ture of the solution has fallen to o (Note 2), a rapid stream of
dry ammonia gas, from a cylinder of compressed gas, is passed
into the solution.
After about fifteen minutes, the theoretical amount of
freshly distilled w-butyl nitrite (95 g. for every 100 g. of phenyl-
hydroxylamine) is added slowly through a dropping funnel
(Note 3). The addition of butyl nitrite usually requires about
one hour (Note 4), during which time the stream of ammonia
gas is continued in order that ammonia may always be in excess.
If this precaution be not observed, a colored product will result.
The temperature of the reaction mixture should be maintained
below 10 and this may be done best by controlling the rate at
which the butyl nitrite is added. An appreciable rise in tem-
19
20 ORGANIC SYNTHESES
perature will cause the volatilization of considerable quantities
of ether and of ammonia (Note 5).
After the butyl nitrite has been added, the reaction mixture
is stirred for about ten minutes longer in order to insure com-
pletion of the reaction, after which the cupferron is filtered off
and washed several times with small portions of fresh ether.
The product is spread on sheets of paper until all traces of ether
have been lost, and is then stored in bottles where it is exposed
to the vapors of ammonium carbonate. This may be done by
protecting each cork with a double sheet of filter paper and
placing a lump of ammonium carbonate between the cork and
the filter paper.
The yield of cupferron from a given weight of phenylhydroxyl-
amine averages 85-90 per cent of the theoretical amount.
2. Notes
1. The solvent ether may be replaced by benzene, but this
modification offers no advantages for the preparation of cup-
ferron on a laboratory scale.
2. The temperature must be kept low. If it is not, the
material is generally colored brown and the reaction does not
run smoothly. Probably the most important factor in securing
successful results is always to have an excess of ammonia present.
3. The butyl nitrite is freshly distilled as a general pre-
caution, because a product which has stood for some time is
often partially decomposed.
4. In the preparation of cupferron, it has been recommended
that the butyl nitrite be added all at one time. This pro-
cedure is satisfactory only when the amount of phenylhydrox-
ylamine used is less than 200 g.; otherwise the reaction becomes
extremely vigorous and an excessive proportion of ether is lost.
The directions given above, on the other hand, are adaptable
for the preparation of large quantities of cupferron. For the
rapid preparation of small quantities of material, the butyl
nitrite may be added all at one time, provided sufficient excess of
ammonia is present.
CUPFERRON 21
5. It is found that 75 per cent of the ether and 95 per cent of
the butyl alcohol used may be recovered, and that one man, work-
ing six to seven hours, is able to prepare 800 g. of cupferron.
The recovered ether may be used over again, provided the fol-
lowing procedure is followed: The phenylhydroxylamine is dis-
solved in a little fresh ether, the solution cooled and treated
with ammonia, then the recovered ether added. This pre-
caution is necessary owing to the presence of some butyl nitrite
in the recovered ether.
3. Other Methods of Preparation
Nitroso-^phenylhydroxylamine, of which cupferron is the
ammonium salt, has been made by the action of sodium nitrite
and hydrochloric acid on /3-phenylhydroxylamine, 1 of hydrogen
peroxide on normal phenykliazotates, 2 of sodium alcoholate and
hydroxylamine on nitrobenzene, 3 of nitric oxide on phenyl
magnesium bromide, 4 and by the action of permonosulfuric acid
on aniline in the presence of amyl nitrite. 5
Cupferron has usually been prepared from a mixture of alkyl
nitrite and /3-phcnylhydroxylamine in the presence of ammonia
in ether or benzene solution/ 1 but it has also been made by the
zinc dust reduction of nitrobenzene in the presence of amyl
nitrite and ammonium hydroxide solution. 7
1 Ber 27, 1435, 1554 (1894); 52B, 1839 (1919); J. Am. Chem. Soc.41, 280 (igig).
2 Ber. 42, 3575 (1909).
3 Ber. 29, 1885 (1896).
4 Ann. 329, 191 (1903).
5 D. R. P. 227,659; Frdl. 10, 126 (1910).
6 Chem. Z. 35, 913 (1911); J. Ind. Eng. Chem. 3, 629 (1911); 12, 799 (1920);
J. Am. Chem. Soc. 41, 280 (igig).
7 D. R. P. 227,659; Frdl. 10, 126 (1910).
IX
DI-p-TOLYLETHANE (unsym.)
2C 6 H 5 CH 3 +CH=CH(HgS04) -
Prepared by J. S. REJCHERT and J. A. NIEUWLAND.
Checked by OLIVER KAMM.
1. Procedure
A 2-1. flask, containing 700 cc. of toluene, 70 cc. of concen-
trated sulfuric acid, and 7 g. of mercuric sulfate, is fitted with a
stirrer, a thermometer reaching into the liquid, and an inlet
tube connected with a gasometer containing acetylene, as
shown in Fig. i (Note i). The flask and its contents are
tared and cooled to 10 before the absorption of acetylene is
begun. The gas from the tank, A , is washed free from acetone
by being passed first through water in the gasometer, B, and
then through the concentrated sulfuric acid wash bottle, C.
The acetylene is absorbed rapidly, with the evolution of
considerable heat. The temperature of the reaction mixture is
maintained at 10-15 by immersing the flask in a freezing mix-
ture. When at intervals the reaction slows down, it becomes
necessary to sweep the system free from air which accumulates
in the flask. The absorption is continued until about 60 g. of
acetylene has been absorbed, which requires a period of about
two hours (Note 2). During the absorption, the mixture turns
first a reddish brown, then a dark brown, and finally almost
black.
The reaction mixture is freed from the acid by washing once
with pure water and then with sodium carbonate solution, to
which some sodium chloride is added to aid the separation of
23
24
ORGANIC SYNTHESES
the hydrocarbon layer. If emulsification takes place, the addi-
tion of ether will remedy the difficulty.
The toluene layer is transferred to a i-l. flask, without drying,
and the unchanged toluene distilled off; the ditolylethane is
then collected over a range of 295-310. There is practically
no intermediate fraction, but a tarry residue of about 75 g.
remains in the flask. Upon redistillation, the ditolylethane is
FIG. i.
collected at 295-300. The yield is 290-310 g. (60-64 per cent
of the theoretical amount) (Note 3).
2. Notes
i. The acetylene is absorbed with unexpected rapidity so
that it is unnecessary to deliver the gas beneath the surface of
the liquid. In an ordinary reaction involving a gas it would
be advisable to use a special stirrer of the type illustrated in
Org. Syn. 3, p. 29, and to deliver the gas beneath the dis-
tributing tube of the stirrer.
DI-/-TOLYLETHANE (unsym.) 25
2. It is scarcely necessary to remove the flask for weighing
until near the end of the experiment, since the volume of acetylene
is known and practically complete absorption takes place. If
a tank of compressed gas is not available, the acetylene may be
prepared from calcium carbide by the usual laboratory methods. 1
3. Subsequent redistillation yields a product boiling prac-
tically over a 2-degree range. The best product was obtained
by a final fractionation under diminished pressure, when the
boiling point was found to be 144-1 45 /8 mm.
4. Xylene, mesitylene, ethylbenzene, and benzene condense
with acetylene in a manner similar to that described above for
toluene, although the yields are usually lower. 2
3. Other Methods of Preparation
Ditolylethane has been obtained also from the reaction
between paraldehyde and toluene in the presence of sulfuric
acid, 3 from the reaction between ethylidene chloride and toluene
in the presence of aluminium chloride, 4 and by heating a-ditolyl-
propionic acid in the presence of lime. 5
l Ct. C. A. 3, 2887 (1909).
2 J. Am. Chem. Soc. 45, 3090 (1933)
3 Bcr 7, 1193 (1874).
4 Ann. 235, 313 (1886).
6 Her. 16, 1476 (1882)
X
ETHYL OXOMALONATE
2 H 5 )2 + 2N2O3 -> CO(CO 2 C 2 H 5 ) 2 +H 2 O+4NO
Prepared by A. W. Dox.
Checked by C. S. MARVEL and R. L. SHRINER.
1. Procedure
INTO a 500-00. Erlenmeyer flask containing 200 g. of ethyl
malonate, and cooled to o by surrounding with cracked ice and
salt, a rapid current of nitrous anhydride is passed. The gas is
generated by dropping concentrated nitric acid through a separa-
tory funnel upon dry arsenious oxide contained in a 500-00.
Florence flask placed upon a tripod and wire gauze. The arseni-
ous oxide should be in lumps about the size of a pea. An empty
flask is inserted between the generator and the absorption flask
and the gas dried by passage through a calcium chloride tube
(Note i). As the evolution of gas slows down, gentle heat may
be applied with a burner. The ethyl malonate becomes dark
green in color. There should be an increase in weight of about
200 g. in two to three hours.
The liquid is left in the freezing mixture for several hours,
then gradually allowed to come to room temperature (Note 2).
Red gases are slowly evolved. After standing for two days or
more at room temperature, the liquid is transferred to a distilling
flask provided with a capillary air intake, and the delivery tube
connected with a water-cooled condenser and receiver. The
distillation is performed under diminished pressure, by the use
of a water pump. Considerable nitric oxide is evolved before
the pressure drops to about 70 mm. (Note 3).
The first fraction consists mainly of water, a little ethyl
acetate, and some ethyl oxomalonate which recombines with the
water to form ethyl mesoxalate. When the pressure has dropped
to 45 mm. and the temperature has risen to 110, the receiver is
27
28 ORGANIC SYNTHESES
changed (Note 4). The main product, ethyl oxomalonate, now
distils at no-i35/45~5o mm. If the oxidation has been com-
plete, very little residue is left (Note 5). Redistillation gives a
golden-yellow liquid boiling between io3-io8/i5 mm. The
yield is 160-165 g. (74-76 per cent of the theoretical amount).
2. Notes
1. The yield of ethyl oxomalonate is decreased if the nitrous
anhydride is not dried.
2. If the temperature is raised too rapidly, the liberation of
gases causes the mixture to boil too vigorously.
3. A motor pump is not recommended because the nitric
oxide is apt to cause corrosion. If too high a vacuum is used at
first, a residue of ethyl iso-nitrosomalonate may remain.
4. The remainder of the distillation must be conducted with
extreme care. As soon as the ethyl oxomalonate has partly
distilled over and the temperature has risen somewhat, the
remaining iso-nitroso compound begins to decompose and some-
times liberates gases so rapidly that the thermometer and capil-
lary tube may be blown out of the flask. If the manometer is
watched closely, and at the first sign of liberation of gas, as
evinced by a sudden increase in pressure, a wet towel is placed
around the flask, the reaction can be slowed down.
5. In case any considerable amount of residue remains above
135 at 45 mm., it is heated at ordinary pressure to a higher
temperature until no more nitric oxide is given off, then distilled
as before.
3. Other Methods of Preparation
Ethyl oxomalonate is obtained from a variety of interme-
diates 1 but the only method which appears of practical value
consists in the oxidation of ethyl malonate by means of oxides
of nitrogen. This reaction, carried out in two steps by Bouveault
and Wahl, 2 was studied by Schmidt 3 and subsequently con-
siderably improved by Curtiss 4 and also by Meyer. 5
1 Beilstein, 3, 769-770 (Fourth Edition). 2 Compt. rend. 137, 196 (1903).
8 Compt. rend. 140, 1400 (1905). 4 Am. Chem. J. 33, 603 (1905); 35, 477 (1906).
6 Bull. soc. chim. (4) 9, 423 (1911); C. A. 5, 3229 (1911).
XI
ETHYL PROPANE-M,2,3-TETRACARBOXYLATE
(C 2 H 5 ONa)
Prepared by H. T. CLARKE and T. F. MURRAY.
Checked by C. S. MARVEL and M. M. BRUBAKER.
1. Procedure
IN a 5-1. flask, fitted with a stirrer, reflux condenser, and
dropping funnel, is placed 1000 g. of absolute ethyl alcohol;
92 g. of sodium, cut into strips, is then added through the con-
denser at such a rate that the alcohol does not boil too vigor-
ously. When all the sodium is in solution, the flask is cooled
and 800 g. of ethyl malonate added through the condenser, with
stirring. The mixture is warmed gently on the steam bath and
700 g. of ethyl fumarate (Note i) added from the dropping
funnel. During this addition the solution is kept boiling gently,
heat being applied if necessary (Note 2) . The mixture is boiled
for one hour after the ethyl fumarate has been added. It is
then cooled and 250 g. of glacial acetic acid is added.
Most of the alcohol is distilled off under slightly reduced
pressure on the steam bath and the residue is poured into suffi-
cient distilled water to dissolve all the solid. The water layer
is separated and extracted four times with carbon tetrachloride,
which is added to the ester layer. The ester-carbon tetrachlo-
ride mixture is washed twice with water and the water washings
extracted once with carbon tetrachloride. The carbon tetra-
chloride is distilled off under atmospheric pressure through a
column, the moisture being carried over simultaneously.
29
30 ORGANIC SYNTHESES
The residue is then distilled under reduced pressure, when
the ethyl propane- 1,1, 2, 3-tetracarboxylate comes over at
i82-i84/8 mm. The yield is 1261-1273 g. (95-96 per cent of
the theoretical amount).
2. Notes
1. The ethyl malonate and ethyl fumarate should be redis-
tilled under reduced pressure, and the material boiling over a
2-degree range should be collected.
2. Heat is developed during the reaction, and the mixture
may be kept boiling by adding the ethyl fumarate at a suitable
rate.
3. Other Methods of Preparation
Now that fumaric and maleic acid are available commercially,
the most convenient method of preparing the above ester con-
sists in condensing ethyl malonate with ethyl fumarate 1 or ethyl
maleate. 2 It has also been prepared by condensing malonic
ester with ethyl chlorosuccinate 3 and with ethyl ethoxysucci-
nate. 4
J Ber. 24, 2889 (1891), J. prakt. Chem. (2) 45, 56 (1892); J. Chem. Soc. 73,
1007 (1898); Ann 341, 102 (1905)
2 J. prakt. Chem (2) 45, 56 (1892).
Ber 23,375Q(i89o).
4 Chem. Zentr. 1903 (II), 943; Ann. 341, 104 (1905).
XII
GLYCINE
CH 2 =NCH 2
CH 2 O+HBr NH 2 CH 2 C0 2 H+NH 4 Br
HBr NH 2 CH 2 CO 2 H + C 5 H 5 N ->
NH 2 CH 2 C0 2 H + C 5 H 5 N - HBr
Prepared by H T CLARKE and E. R. TAYLOR.
Checked by ROGER ADAMS and W. F. TULEY.
1. Procedure
IN a 5-1. flask fitted with a downward condenser, are placed
340 g. of methylene aminoacetonitrile (p. 47) and 2500 g. of
48 per cent hydrobromic acid (Note i). The mixture is heated
on the steam bath for three hours (Note 2). The pressure in
the apparatus is then reduced and dilute acid and formaldehyde
are distilled into a water-cooled receiver until the separation of
ammonium bromide from the reaction mixture causes bumping.
This occurs when approximately half of the liquid has been dis-
tilled over. The ammonium bromide is filtered from the hot
liquid and washed with a small amount of cold water; the
filtrates are returned to the flask and distillation continued as
nearly as possible to dryness (Note 3). The residue is dissolved
in 2 1. of cold methyl alcohol and filtered; to the filtrate is added
350 cc. of pyridine, with vigorous shaking (Note 4).
The mixture is allowed to stand over night and the precipi-
tated glycine filtered off and washed with methyl alcohol
(Note 5) until the washings are free from bromides. The prod-
uct is dissolved in 300 cc. of boiling distilled water and the solu-
tion filtered with the use of a little decolorizing carbon; the
filtrate is allowed to cool to 40-50, when 1500 cc. of methyl
alcohol is added with hand stirring. If the product is colored,
the procedure, just described, of dissolving in water and repre-
cipitating with methyl alcohol is repeated. The glycine that
31
32 ^ ORGANIC SYNTHESES
separates is filtered off when the mixture is cold and washed with
methyl alcohol until a sample (Note 6) is found to be free from
ammonia on testing with Nessler solution (Note 7). If a second
precipitation is made, the glycine is practically free from ammo-
nium salts and washing with methyl alcohol is unnecessary.
Not more than i 1. of methyl alcohol should be necessary for
this purpose; if positive tests continue to be obtained, an
ammonia-free product may be secured by treating the aqueous
solution for a short time with a water-softening zeolite, filtering
and crystallizing or precipitating with alcohol.
The yield is 115-140 g. (31-37 per cent of the theoretical
amount) of a colorless product which melts with decomposition
at 225-230 (Note 8).
The distillate from the reaction mixture may be redistilled
under atmospheric pressure with the use of a column; the
fraction boiling at 125-126 may be collected, when one-third
to one-half the amount of hydrobromic acid originally taken can
be recovered. The foreruns contain formaldehyde.
2. Notes
1. If preferred, 3000 g. of 40 per cent acid may be taken.
Hydrobromic acid is employed in preference to other mineral
acids on account of the high solubility of ammonium bromide in
methyl alcohol.
2. Hydrolysis takes place readily, with a slight evolution of
heat, so that actual boiling over a free flame is unnecessary.
3. The residue consists of a syrup (largely glycine hydro-
bromide) mixed with crystals of ammonium bromide. It has a
strong odor of formaldehyde.
4. A technical grade of pyridine may be employed if this is
colorless and distils not lower than 100 nor higher than 140.
5. Ammonium bromide dissolves in about eight times its
weight of methyl alcohol. It is much less soluble in absolute
ethyl alcohol, requiring about 30 parts of that solvent.
6. The sample should be taken from the lower part of the
cake on the funnel by means of a glass tube, since the upper
layers become free of impurities first.
GLYCINE 33
7. The sample of glycine must be dry before testing, as
traces of impurities generally present in the methyl alcohol give
a precipitate with Nessler solution. To carry out the test,
0.1-0.2 g. of dry product is dissolved in 3 to 5 cc. of distilled
water containing a few drops of sodium hydroxide solution, and
i cc. of Nessler solution is added.
8. A further small quantity of impure glycine can be iso-
lated by concentrating the filtrates obtained on recrystalliza-
tion. The liquors from the first precipitation, containing
ammonium bromide, pyridine hydrobromide, excess pyridine,
and alcohol-soluble by-products, may be treated as follows:
The mixture is first acidified with mineral acid and the methyl
alcohol recovered by distillation with a column. The residue
is rendered strongly alkaline and the bulk of the ammonia
removed by boiling under a reflux condenser; wet pyridine can
be recovered by downward distillation and treatment of the dis-
tillate with solid sodium hydroxide.
3. Other Methods of Preparation
Glycine hydrochloride has been prepared by the action of
hydrochloric acid upon hippuric acid, 1 upon aminoaceto-
nitrile, 2 upon methylene aminoacetonitrile, 3 and upon ethyl
phthaliminoacetate; 4 its conversion into free glycine by methods
involving silver or lead oxides is apt to be troublesome. The
classical method of preparing glycine by the interaction of
chloroacetic acid and ammonia 5 is unsatisfactory, owing to the
laborious process of isolation through the copper salt, which,
moreover, rarely gives a product entirely free of ammonia.
The hydrolysis of methylene aminoacetonitrile by successive
treatments with barium hydroxide and sulfuric acid 6 furnishes
a more satisfactory method, but the final product is seldom
entirely pure, partly owing to the difficulty in obtaining pure
barium hydroxide. The same objection applies to the hydrolysis
of aminoacetonitrile by means of barium hydroxide. 7
1 J prakt. Chem. (2) 37, 157 (1888). 6 Ann. 266, 205 (1891).
2 Ann. 278, 236 (1894). 6 Biochem. J. 16, 702 (1922).
Ber. 27, 60 (1894). 7 Ann. 278, 237 (1894).
Ber. 22, 428 (1889).
XIII
HYDROXYHYDRO QUINONE TRIACETATE
O=C G H 4 =0+2(CH a CO)2O-> OCOCH ;i
1-OCOCH 3
+ CH 3 COOH
OCOCHs
Prepared by K B. VLIET.
Checked by ROGL.R ADAMS and H. O. CALVERY.
1. Procedure
TWELVE grams of concentrated sulfuric acid is added to
1 80 g. of acetic anhydride in a 6oo-cc. beaker, after which 60 g.
of benzoquinone (Note i) is added gradually in small portions
with constant mechanical stirring. The temperature rises and
should be held at 40-50 during the addition of the quinone.
A temperature higher than 50 leads to decomposition of the
product while a temperature lower than 40 causes a much
slower reaction. Good temperature control can be obtained by
using care in adding the quinone and by the use of a cooling
bath and efficient stirring. The reaction goes smoothly and
does not evolve an excessive amount of heat.
After all the quinone has been added, the solution is allowed
to stand. It should be watched closely at first to see that the
temperature does not rise above 50, but at the same time it is
well not to cool it below 40. When the mixture starts to cool
of its own accord, a precipitate begins to form. As soon as the
mixture has cooled to about 25 (Note 2), it is poured into
750 cc. of cold water, whereupon a white precipitate separates.
This is cooled to about 10 and filtered off with suction. The
35
36 ORGANIC SYNTHESES
product is recrystallized from 250 cc. of 95 per cent ethyl aclohol
and dried. The drying is best done in a vacuum desiccator,
through which a very small stream of air is allowed to sweep.
Calcium chloride is the best drying agent.
The product is practically white and rather granular; it
melts at 96-97. The yield is 120-123 g. (85-87 per cent of the
theoretical amount). The product is fairly reactive and tends
to decompose upon standing (Note 3), especially if care be not
used in drying and handling. If it is to be used as a starting
material for other syntheses, it is advisable to use it as soon as
possible.
2. Notes
1. The quality of the product depends to a large extent upon
the purity of the benzoquinone; if the latter is dark, it is advis-
able to crystallize it from benzene before using it. (See Org.
Syn. 2, 86.)
2. It is quite desirable to have the reaction mixture cooled
to about 25 before it is added to the water. If it is warm when
added to the water, an oil will separate which solidifies slowly
in the form of lumps.
3. The hydroxyhydroquinone triacetate keeps quite satis-
factorily in an atmosphere of carbon dioxide.
3. Other Methods of Preparation
The method described above is essentially the same as that
of Thiele, 1 which has been patented by F. Bayer and Company. 2
Hydroxyhydroquinone triacetate has also been obtained by
acetylating hydroxyhydroquinone formed by the alkali fusion
of hydroquinone. 3
1 Ber. 31, 1247 (1898); Gazz. chim. ital. 40 (2) 349 (1910).
2 D. R. P. 101,607 and 107,508; Frdl. 5, 155-6 (1898;.
3 Monatsh. 5, 590 (1884).
XIV
o-IODOPHENOL
2HOC 6 H 4 HgCl+2l 2 - Hgl2+HgCl2+2lC6H 4 OH
Prepared by F C. WHITMORE and E. R. HANSON.
Checked by J. B. CONANT and R. M. GRANARA.
1. Procedure
A 2-1. round-bottom short-neck flask is equipped with a
glass mechanical stirrer. A suspension of 165 g. of 0-chloro-
mercuriphenol (p. 13) (m.p. 147 or higher) in 500 cc. of chloro-
form is placed in the flask and treated with 127 g. of iodine, the
stirring being continued until a small sample on nitration shows
no unreacted iodine. This requires from one to two hours.
The solid inorganic mercury compounds are removed by suction
filtration. The filtrate is distilled from a i-l. distilling flask on
the water bath to remove most of the chloroform, which is
saved for later runs (Note i). The residual liquid is shaken
vigorously with a solution of 5 g. of potassium iodide in 10 cc.
of water, to remove dissolved mercuric iodide. The heavier
layer, which still possesses a reddish color, is transferred without
drying to a 2oo-cc. Claisen flask and distilled under diminished
pressure. At first a small amount of chloroform and water distils
over, after which the higher-boiling material is collected in a
separate receiver. Small amounts of inorganic mercury com-
pounds remain in the flask (Note 2).
The 0-iodophenol solidifies upon cooling. The yield of
material melting at 32-34 is 70 g. (63 per cent of the theoretical
amount). The product obtained in this way is slightly yellow.
If a purer product is desired, it may be redistilled in vacuo.
37
38 - ORGANIC SYNTHESES
Most of the crude material will distil over a 5-degree range
(b.p. i3o/i8 mm. and i&6/i6o mm., m.p. 43).
2. Notes
1. About 460 cc. of chloroform can be recovered, the time
required being one hour.
2. The first distillation of the iodophenol should be carried
out under a good vacuum, 40 mm. or lower. The redistillation
may be conducted at a higher pressure if desired.
3. Since the iodophenol has a most persistent odor, care
should be exercised in working with it. A solution of bromine
in glycerol may be used as an antidote for burns from the iodo-
phenol (p. 14).
3. Other Methods of Preparation
0-Todophenol has been made by diazotization from 0-amino-
phenol l and from 0-iodoaniline. 2 It has been obtained by
heating 0-iodosalicylic acid. 3 Mixed with its para isomer and
diiodophenol, it has been made by treating a dilute phenol
solution with iodine and iodic acid, 4 and it has also been obtained
from an alkaline solution of phenol and iodine in the presence of
mercuric oxide, 5 and from dry sodium phenol ate and iodine in
carbon disulfide. 6
1 Ber. 8, 820 (1875); Ann. 241, 68 (1887).
2 Chem. Zentr. 1910 (II;, 304.
3 Ann. 120,315 (1861).
4 Z. Chem. 1866, 662, 1868, 322.
6 Ber. 2, 523(1869); 6,1251 (1873).
8 Ber. 16, 1897 (1883), 20, 3363 (1887).
XV
KETENE
CH 3 COCH 3 -> CH,i=
1. Procedure
Prepared by C. D. KURD.
Checked by OLIVER KAMM.
A. Preparation of ketcnc. The arrangement of the appara-
tus is shown in Fig. 2 (Note i). The graduated separatory
funnel, shown in the diagram, rilled with 125 cc. of commercial
acetone, leads into a 5oo-cc. round-bottom flask which, in turn,
is connected by gas-tight joints (Note 2) to a glass combustion
tube filled with broken porcelain, a spiral or bulb condenser, a
two-way stopcock, and a reaction flask. In the reaction flask
is placed the material with which the ketene is to react (Note 3) .
A second reaction flask may be placed in series, if desired, to
ascertain if any ketene escaped reaction in the first flask.
Prior to either of these steps, fourteen of the twenty burners
of the combustion furnace are lighted (Note 4) and tiles are
placed over the lighted burners, which finally must be adjusted
to yield a maximum temperature. The first two and last four
burners are unused.
When the furnace is fully heated, boiling water is placed
beneath the round-bottom flask and cold water passed through
the condenser. Acetone is now dropped in at the rate of 3-4 cc.
per minute. About half the acetone should be recovered as
distillate in cylinder B (Note 5) . Ketene, admixed with methane,
carbon monoxide, and ethylene, passes into the reaction flasks
(Note 6) in 25-29 per cent yields. The flow may be interrupted
at will by checking the acetone flow.
39
40
ORGANIC SYNTHESES
B. Preparation of acetanilide. Since ketene is a highly
reactive gas, it is usually prepared for immediate consumption
instead of being isolated as such. It reacts with various groups
which contain hydrogen, such as hydroxyl, amino, mercaptan,
hydroxylamino, etc., forming acetyl derivatives.
Twenty-five grams of aniline is placed in the reaction flask,
D, and 50 cc. of dry ether added as solvent (Note 7). A second
reaction flask is connected at C, in which is placed 5 g. of aniline,
5
FIG. 2.
dissolved in 20 cc. of ether. This prevents the escape of ketene
vapor at the beginning and at the close of the operation (Note 5).
In all, 85 cc. of acetone is passed through the apparatus, 39 cc.
of which is recovered as distillate. Therefore, 44 cc. (or 35 g.)
of acetone is decomposed. The duration of the run is about
thirty minutes. Twenty-one grams of acetanilide, which cor-
responds to a yield of 25.8 per cent, based upon the amount of
acetone decomposed, is isolated from the reaction mixture.
2. Notes
i. The apparatus. A graduated dropping funnel and a
graduated cylinder for the distillate are chosen because of con-
venience in determining the volume of decomposed acetone.
KETENE 41
The bulb (or spiral) condenser is chosen because of its effi-
ciency. With an ordinary condenser, it is necessary to insert
two U-tubes, cooled by ice, between the condenser and the
reaction flask, to remove all the acetone from the ketene. In
many reactions, however, this admixed acetone will do no harm.
This part of the apparatus is designed to eliminate the loss of
ketene by solvent action, prior to its entry into the reaction
flask.
A wide-mouth delivery tube in the reaction flask is essential
to prevent clogging, when a solid product is formed. Automatic
stirring in the reaction flask may be used to advantage in certain
instances. There is constant agitation, of course, as the gaseous
decomposition products bubble through.
Either Scotland glass or Pyrex is satisfactory for the com-
bustion tube. An estimate of the temperature is 650 (Note 4).
The life of the tube is lengthened if it rests upon a layer of thin
asbestos paper. The tube is filled with pieces of broken porce-
lain, to serve as a " heat reservoir "; there is no catalytic effect.
The porcelain blackens during the reaction.
2. Care in assembly. Since this is a gaseous reaction, it is
essential that the apparatus be free from leaks; thus, corks are
eliminated wherever possible. The ends of the combustion tube
and the top of the condenser are drawn to the diameter of the
connecting tubes and joined by a piece of thick-walled rubber
tubing. Care should be taken to have the ends of the glass
tubes come into contact. The rubber tube situated between
the furnace and condenser is protected by the asbestos screen,
but a further essential precaution is taken, namely, that this
end of the combustion tube extend a considerable distance from
the furnace.
The stoppers in the reaction flask and at the top of the drop-
ping funnel are of rubber; the other two are well-selected corks,
bored perfectly and painted both inside and out with water-
glass, one day previous to being used.
3. The apparatus may be calibrated by allowing the ketene
to react with sN alkali and titrating the excess alkali with acid.
4. With an electric combustion furnace, wherein a tempera-
42 ORGANIC SYNTHESES
ture of 695-705 is maintained, consistent yields of 35-40 per
cent ketene are produced. The best rate of flow in such a case
is 4-6 cc. per minute, with recovery of 60-80 per cent of the
original acetone as distillate. Although yields of ketene rang-
ing above 45 per cent have been obtained frequently with this
apparatus, they could not be duplicated consistently.
5. The thermal decomposition of ketene into carbon mon-
oxide and ethylene is prevented, as far as possible, by the rapid
removal of ketene from the hot tube, which is accomplished by
the undecomposed acetone vapor. About half the acetone
originally used should be collected unchanged as distillate by
the vertical condenser. The yield of ketene will fall consider-
ably if less distillate is formed.
6. Ketene gas is very irritant when breathed, and hence
proper cautions should be taken to avoid inhalation.
7. An ice bath surrounding the reaction flask is usually
employed, not only to prevent the vaporization of the solvent,
but also to promote a greater solubility of ketene.
3. Other Methods of Preparation
In addition to the above method, based upon the work of
Schmidlin and Bergman 1 as modified by Hurd and Cochran, 2
ketene has been prepared by the pyrogenic decomposition of
acetic anhydride, 3 of ethyl acetate, and of triacetin. 4 In the
last instance, acrolein and acetic acid are formed simultaneously,
Ketene has also been formed by the action of zinc upon an
ethereal solution of bromoacetyl bromide/ 3 Carbon monoxide
and diazomethane, diluted with ether, when passed through a
quartz tube at 400-500, yield ketene and nitrogen. 6
iBer. 43, 2821 (1910).
2 J. Am. Chem. Soc. 45, 515 (1923).
3 J. Chem. Soc. 91, 1938 (1907); 97, 1968 (1910).
Ber. 47, 2393 (1914).
6 Ber. 41,594(1908).
6 Ber. 45, 508 (1912).
XVI
0-METHYL ANTHRAQUINONE
C0 2 H
(H 2 S0 4 )
/\ /
CO'
/ \/ \y x/v"o
H 2
Prepared by L. F. Ficser.
Checked by ROGER ADAMS and R. L. SIIRINER.
1. Procedure
THE />-toluyl-0-benzoic acid which is obtained from 100 g.
of phthalic anhydride (p. 73), and which should weigh 157 g.,
is mixed with 1400 g. of fuming sulfuric acid (20 per cent anhy-
dride) (Note i) in a 2-1. flask protected by a calcium chloride
tube; and the mixture is heated on the steam bath for two
hours with occasional shaking (Note 2). The clear, deep red
solution is poured when cold upon cracked ice in a 4-!. beaker.
The methyl anthraquinone separates and is digested for twenty
minutes by passing in steam, after which it is filtered by suction.
A flannel cloth is used in the filter, or a filtros plate may be
cemented into a Buchner funnel with water-glass. The pre-
cipitate is washed well with hot water, after which it is returned
to the beaker and digested as before with hot water to which
is added a slight excess of ammonia, beyond that required to
neutralize any acid present.
The product is filtered and dried to constant weight. The
filtrate will be clear and will give no precipitate with hydro-
chloric acid if the conditions of condensation have been correct.
The 0-methyl anthraquinone is pale tan in color and weighs
from 118 to 130 g. (86-95 per cent of the theoretical amount,
based upon the weight of acid taken). It is practically pure,
melting at 173. Upon crystallization from alcohol in the
presence of bone-black, it forms long, silken, almost colorless
needles, melting constantly at 173.5 (176 cor.).
43
44 ' ORGANIC SYNTHESES
2. Notes
1. Some investigators have used concentrated instead of
fuming sulfuric acid for the condensation, but the yield is usually
low and the product is always colored bright yellow by some
impurity which cannot be removed by crystallization.
2. The time allowed for condensation may be shortened to
one-half, without affecting the yield, by maintaining the tem-
perature at 125-130 for this length of time.
3. Other Methods of Preparation
/3-Methyl anthraquinone has been obtained by the oxida-
tion of /3-methyl anthracene by several investigators; l and
material of the same origin, obtained by the benzene-extraction
of crude commercial anthraquinone, 2 has been fully described.
As regards the synthesis from phthalic anhydride and toluene,
both the preparation and properties of />-toluyl-o-benzoic acid 3
and the complete synthesis 4 have been the subject of several
papers. This acid has also been prepared from 0-carbomethoxy
benzoyl chloride and toluene. 5 The phthalic anhydride syn-
thesis of anthraquinone derivatives in general has received con-
siderable attention. An account of this work, together with
extensive references, is given by Barnett. 6
The following unimportant preparative methods may be
mentioned: the production of /3-methyl anthraquinone by the
reduction of 2-bromo-3 -methyl anthraquinone; 7 the oxidation
of /3-methyl anthracene-7-carboxylic acid; 8 and the reduction
of 2 -methyl anthraquinonyl-i-diazonium sulfate. 9
1 Ber. 8, 675 (1875); J. prakt. Chem. [2] 79, 560 (1909); [2] 82, 232 (1910); [2]
83, 210 (1911); Ann. chim. phys. [8] 20, 445 (1910).
2 J. Chem. Soc. 66, 843 (1894); Ber. 10, 1485 (1877); 15, 1820 (1882); 16, 696,
1632 (1883).
3 Bull. soc. chim. [2] 35, 505 (1881); [3] 17, 969 (1897); Ann. chim. phys. [6]
14, 447 (1888); Monatsh. 32, 639 (1911); J. Am. Chem. Soc. 43, 1965 (1921).
4 J. prakt. Chem. [2] 33, 319 (1886); [2] 41, 4 (1890); Ann. 234, 239 (1886);
299, 300 (1898); 311, 180 (1900); Ber. 28, 1134 (1895); 41, 3632 (1908); J. Russ.
Phys. Chem. Soc. 46, 1067 (1914).
6 J. Am. Chem. Soc. 43, 1922 (1921).
8 Anthracene and Anthraquinone, pp. 130-141, Van Nostrand (1921).
7 Ber. 45, 796 (1912).
8 Ber. 46, 1214 (1912).
Ber. 46, 1646 (1913).
XVII
/3-METHYL ESCULETIN
(6, 7-Dihydroxy-4-methyl-l, 2-benzopyrone)
OCOCHs
OCOCHs
CH 3 COCH 2 C02C 2 H5 + 2H 2
OCOCH 3 CH 3
I
HO
3 CH 3 C0 2 H + C 2 H 5 OH
//
Prepared by E. B. VLIET.
Checked by ROGER ADAMS and E. E. DREGER.
1. Procedure
A SMOOTH, uniform paste is made by thoroughly mixing 60 g.
of ethyl acetoacetate (Note i) and 114 g. of hydroxyhydro-
quinone triacetate (p. 35). This requires several minutes of
stirring. To this mixture is added 450 cc. of 75 per cent sul-
furic acid (Note 2). The paste slowly dissolves with the evolu-
tion of heat, giving a deep red solution; the latter is heated on
a warm bath with occasional stirring until it reaches 80, at
which temperature it is maintained for one-half hour. It is
then allowed to cool to room temperature and poured into
1850 cc. of cold water. The resulting mixture is cooled to room
temperature, filtered with suction, and the precipitate washed
with cold water to free it from excess acid. The /3-methyl
esculetin thus obtained is dried at 100 and is generally gray in
color. The yield is about 80 g. (92 per cent of the theoretical
amount).
45
46 * ORGANIC SYNTHESES
A pure product may be obtained by dissolving with the aid
of heat and stirring 100 g. of /3-methyl esculetin in a solution of
200 g. of borax in 700 cc. of water. The solution obtained is
filtered while hot and then cooled, whereupon the esculetin
borate separates (Note 3). This is filtered off and dissolved in
1800 cc. of water, and the solution thus obtained added to 50 g.
of concentrated sulfuric acid in 500 cc. of water. /3-Methyl
esculetin separates and, after the mixture has been cooled, is
tillered, washed, and dried. From 100 g. of the crude material,
85 g. of pure product melting at 272-274 (uncor.) is obtained.
This is generally nearly colorless but occasionally possesses a
slight grayish tinge.
2. Notes
1. In order to obtain a fairly pure product without recrys-
tallization, the intermediate ethyl acetoacetate and hydroxy-
hydroquinone triacetate must be pure.
2. It is important to use 75 per cent sulfuric acid in this
reaction, because more concentrated acid gives a very dark
product and a lower yield, while more dilute acid will not induce
the reaction.
3. The exact nature of the precipitate has nol been deter-
mined.
3. Other Methods of Preparation
/3-Methyl esculetin was first prepared by Pechman, 1 by con-
densing hydroxyhydroquinone triacetale and ethyl acetoacetate
by allowing them to stand for twenty-four hours with cold con-
centrated sulfuric acid. This method gave a dark product,
difficult to purify, and a yield of 60-65 P er cent. Pechman also
used boiling alcoholic zinc chloride as the condensing agent in
place of sulfuric acid but does not state the yield thus obtained.
Bargellini and Martegiani ~ used 73 per cent sulfuric acid
and heated on the water bath. They obtained an improved
yield of a product of better quality. Zinc chloride in acetic
acid proved to be unsatisfactory.
^er. 34, 423 (1901).
2 Gazz. chim. ital. 41 (2), 613 (1911).
XVIII
METHYLENE AMINOACETONITRUE
(a-Hydroformamine Cyanide *)
NaCN+NH 4 Cl + 2 HCHO -> CH2=NCH 2 CN+NaCl+2H 2
Prepared by ROGER ADAMS and W. D. LANGLEY.
Checked by H T. CLARKE and E. R, TAYLOR.
1. Procedure
IN a 5-!. round-bottom flask, fitted with a mechanical stirrer
and surrounded by an ice-salt bath, are placed 1500 cc, of tech-
nical formaldehyde (sp. gr. 1.078/20) (Note i) and 540 g. of
ammonium chloride. A thermometer is placed in the liquid,
which is cooled to o. This temperature is maintained through-
out the entire reaction (Note 2). Stirring is commenced
(Note 3) and a solution of 490 g. of 98 per cent sodium cyanide
in 850 cc. of water is dropped into the mixture of ammonium
chloride and formaldehyde at such a rate (about 90 drops per
minute) that at least six hours will be required for this addition.
When one-half the sodium cyanide solution has been added,
all of the ammonium chloride will be in solution. At this point,
the addition of 380 cc. of glacial acetic acid is started at such a
rate (2 to 2.5 cc. per minute) that the addition of both the acid
and the remainder of the sodium cyanide solution will be com-
pleted at the same time. The methylene aminoacetonitrile
begins to separate in white crystals shortly after the addition of
the glacial acetic acid has commenced. After all the sodium
cyanide solution and acetic acid have been added, the mixture
is stirred for an hour and a half longer; then the precipitate
* The actual molecular formula is C 9 Hi 2 N 6 . Johnson and Rinehart, J. Am.
Chem. Soc. 46, 768, 1653 (1924).
47
48 * ORGANIC SYNTHESES
is filtered off, transferred to a beaker, and stirred with 1.5 1.
of water. The product is filtered with suction, washed with
500 cc. of water (Note 4), and dried on filter paper. The yield
is 410 to 475 g. (64-74 per cent of the theoretical amount) of a
product of which the melting point is 129 (Note 5).
2. Notes
1. The formalin contains 35 per cent formaldehyde by weight,
as determined by specific gravity. It should contain no sus-
pended paraformaldehyde.
2. During the reaction, the temperature should be kept as
near o as possible and should never rise above 5. If the
temperature goes higher, a heavy oil is sometimes obtained
instead of the crystalline product. It is not difficult to main-
tain the low temperature when the formaldehyde and ammo-
nium chloride are cooled to o before any of the sodium cyanide
is added.
3. In order to obtain good yields, the stirring must be vigor-
ous throughout the entire reaction.
4. With careful washing, 500 cc. of cold water should be
sufficient to remove all chlorides.
5. For most purposes, the product is pure enough as it is
obtained from the reaction mixture, but it may be crystallized
from water. This recrystallization is, however, attended with
considerable loss.
3. Other Methods of Preparation
Methylene aminoacetonitrile has been prepared by the
action of formaldehyde on aminoacetonitrile, 1 and by the action
of formaldehyde on a mixture of ammonium chloride, potassium
cyanide, and acetic acid. 2
1 J. prakt. Chem. (2) 65, 192 (1902).
2 Ber. 27, 59 (1894); 36, 1507 (1903); 43, 868 (1910); J. Am. Chem. Soc. 768,
1653 (1924).
XIX
NICOTINIC ACID
TT
CioH 14 N 2 + (HN0 3 ) ' ' 2tl
Prepared by S. M. MCELVAIN.
Checked by J. B. CON ANT and B. B. CORSON.
1. Procedure
IN a 5-!. round-bottom flask is placed 4 kg. of C.P. concen-
trated nitric acid (sp. gr. 1.42) (Note i). To this is added, in
25-cc. portions, 210 g. of nicotine (Note 2). The addition should
be made carefully in order that local heating may not occur and
material be lost. After each addition of nicotine, the flask
should be shaken in order to insure a homogeneous solution.
The addition of the nicotine causes the temperature of the liquid
to rise somewhat but not sufficiently to cause evolution of nitro-
gen dioxide. The flask is placed on a steam bath under a hood
and heated until the liquid reaches a temperature of 70. It is
then removed and the reaction allowed to continue spontane-
ously (Note 3), heat enough being evolved to cause the liquid to
boil. The boiling ceases after one hour but the flask is replaced
upon the steam bath for ten to twelve hours, during which time
there is a more or less continuous evolution of oxides of nitrogen.
The contents of the flask are then poured into an evaporat-
ing dish and evaporated almost to dryness on the steam bath
(about ten hours). The purification which follows is best
carried out with the product of two runs such as have been
described above.
After the evaporation of most of the liquid, the nicotinic
acid nitrate from two runs is transferred to a 1.5-!. beaker,
400 cc. of distilled w r ater is added (Note 4) and the mixture is
heated until complete solution results. On cooling, the nico-
tinic acid nitrate separates as yellow granular crystals and is
49
50 ORGANIC SYNTHESES
filtered off. To obtain it absolutely pure, it may be recrystal-
lized in a way similar to that just described but with the use of
bone-black. It contains one molecule of water of crystalliza-
tion and has a melting point of 190-192 (cor.). The yield is
420-460 g. (85-91 per cent of the theoretical amount).
The 420-460 g. of crude nicotinic acid nitrate from two runs
(not necessarily dry) is dissolved in 900 cc. of boiling water in a
3-1. beaker and 800 g. of crystalline disodium phosphate
(Na 2 HP04- i2HoO) added with constant stirring. The result-
ing thick mixture is stirred and heated almost to boiling for five
minutes and then allowed to cool. The mixture is finally chilled
to o by an ice bath. It is well to stir occasionally during the
crystallization to prevent the formation of too solid a cake of
crystalline material. The nicotinic acid is filtered off upon a
i5-cm. Buchner funnel and washed with three zoo-cc. portions
of cold water.
The yield is 260-300 g. of material containing a small amount
of mineral salts but otherwise nearly pure. It can be purified
further by recrystallization from 2.5 to 3.5 1. (Note 4) of hot
water, 150-180 g. of material, which melts at 230-232 (cor.),
being obtained. The yield of recrystallized material is 50-60
per cent of the theoretical amount, based upon the nicotine em-
ployed.
The recrystallization is the least satisfactory part of this
procedure and involves the greatest apparent loss of material;
the product before recrystallization is sufficiently pure for most
purposes. By evaporation of the mother liquors, 40-45 g. of
pure nicotinic acid may be obtained, making the total yield of
pure material 190-225 g. (63-74 per cent of the theoretical
amount); in addition, a small amount of somewhat less pure
material is recovered.
2. Notes
1. Fuming nitric acid, the use of which is advised in the
literature, is not as convenient to use and gives no better results
than concentrated nitric acid.
2. A product of loo per cent purity gives no better results
NICOTINIC ACID 51
than does the crude 95 per cent material used in this experiment.
The nicotine was purchased from the Hall Tobacco Company,
of St. Louis, Mo.
3. If the nicotine and nitric acid mixture is merely placed on
a steam bath and allowed to heat without control of the tempera-
ture, an occasional run will react violently, with loss of material.
4. The amounts of solvent given for the various recrystal-
lizations are those which give best yields and it is advisable to
follow them as closely as possible.
5. Nicotinic acid hydrochloride may be obtained directly
from the nitrate by heating on a steam bath 460 g. of crude
nitrate with 1000 cc. of concentrated hydrochloric acid (sp. gr.
1.19). After six to eight hours, the evolution of gas ceases and
the liquid is evaporated under diminished pressure. The dry
salt is again treated with 500 cc. of hydrochloric acid and heated
for five hours and then evaporated as before.
After the salt has been again obtained, it is dissolved in 400 cc.
of hot water and the solution diluted with four times its volume
of 95 per cent alcohol. Upon cooling and stirring, the hydro-
chloride, melting at 273-274, is obtained in a yield of 245-
250 g. An additional quantity of 75-80 g. may be obtained
from the mother liquors.
3. Other Methods of Preparation
Nicotinic acid has been prepared by the oxidation of nicotine
with nitric acid. 1 It has also been prepared by the action of
potassium permanganate upon /3-picoline, nicotine, lutidine,
0-phenyl pyridine, and -dipyridyl 2 and by the action of
chromic acid upon nicotine and 0-phenyl pyridinecarboxylic
acid. 3
It may also be obtained by heating quinolinic acid 3 and
certain other pyridine dicarboxylic acids. 2 The nitrile has been
prepared by heating sodium /3-pyridinesulfonate with potassium
cyanide. 4
1 Ann. 166, 330 (1873); Ber. 34, 702 (1901); Chem. Zentr. 1898 (I), 677,
2 Beilstein 4, 143 (1899); 4*, 108 (1906).
3 Rec. trav. chim. 1, 121 (1882); Arch. Pharm. 240, 353 (1902).
4 Ber. 15,63 (1882).
XX
PENTAERYTHRITOL
(Tetra-hydroxymethyl methane)
8CH 2 O+2CH 3 CHO+Ca(OH) 2 - 2C(CH 2 OH)
Prepared by CHEMICAL LABORATORY, PICATINNY ARSENAL.
Checked by H. T. CLARKE and Ross PHILLIPS.
1. Procedure
IN a 6-gal. crock provided with an efficient stirrer are placed
10.5 1. of water, 5600 g. commercial (35-40 per cent) formalde-
hyde, and 630 g. of acetaldehyde (b.p. 20-22). To this mix-
ture is added, during the course of one-half hour, with constant
mechanical stirring, 475 g. of high-grade quicklime to which
enough water has been added to cause the disintegration of
lumps by slaking. This lime must be in the form of a fine
powder (Note i). During the addition, the temperature of the
mixture is raised by injection of live steam (Note 2) to 60-65,
and is held at this point for two hours after all has been added
(Note 3).
The mixture is then cooled by surrounding the crock with
cold water, and about 1700 g. of cold 50 per cent sulfuric acid is
added, until a filtered sample just fails to yield a further precipi-
tate of calcium sulfatc upon the further addition of sulfuric acid.
The calcium sulfate is filtered off and washed with cold water.
A saturated aqueous solution of oxalic acid is cautiously added
to the filtrate until a filtered sample gives no test for calcium
salts in solution (Note 4).
The resulting solution, which should now be clear and lemon
yellow in color (Note 5) , is concentrated under reduced pressure
on the steam bath (Note 6, Fig. 3) until the volume is reduced
53
54
ORGANIC SYNTHESES
to 3.5-4 1. It is then cooled and the crystalline precipitate
filtered off by suction and washed with methyl alcohol or 95
per cent ethyl alcohol (Note 7) in small portions, until the wash-
ings are colorless. The product thus obtained weighs 900-960 g.
and melts without decomposition at 250-252 (Note 8). The
mother liquor and washings are further concentrated (Note 9)
to a syrup, from which a second crop of 100-250 g. is obtained
upon cooling. This is washed as before with alcohol but pos-
To Pump
FIG. 3.
sesses a slightly yellow color and must be recrystallized from
an equal weight of water. The total yield of product of m.p.
250-252 is 975-1055 g. (50-54 per cent of the theoretical
amount) .
2. Notes
1. The quicklime may be ground mechanically before addi-
tion, but this is less convenient than disintegrating it by the
cautious addition of water.
2. If mechanically powdered quicklime is used, the use of
steam is unnecessary, and the temperature is to be controlled
PENTAERYTHRITOL 55
by the rate of addition. The use of heating and cooling coils
in the crock is most convenient if available; such coils may
safely be of iron tubing. Temperatures above 65 result in a
lower yield of less pure product.
3. After the mixture has been maintained at 60-65 for a
period of about one hour, the initial gray color undergoes a rapid
change to yellow. This change is accompanied by a marked
diminution in the odor of aldehydes.
4. The presence of only a slight excess of oxalic acid is per-
missible, although it is essential to, remove all calcium salts
since they would contaminate the final product; but small
quantities of free oxalic acid do not interfere with the subsequent
operations and are removed in the mother liquors.
5. The liquor may profitably be treated with decolorizing
carbon at this point.
6. The apparatus shown in Fig. 3 has been found convenient
for such evaporations under reduced pressure. The distillation
is started with 3.5-4 1. in the 12-!. flask, and the level of liquid
is maintained by controlling the rate of addition by means of a
screw clamp. A 2-1. flask has been found satisfactory for the
condensing intermediate receiver, provided the outside be com-
pletely wetted by the cold water.
7. Nearly i 1. of ethyl alcohol is required. Pentaery-
thritol is insoluble in the cold alcohol, which dissolves the sticky
polymerized aldehydes obtained on concentrating the solution.
8. The product is sufficiently pure for most purposes, but
may be recrystallized from slightly more than an equal weight
of boiling water.
9. The washings may be collected separately and the alcohol
recovered by distillation from a steam bath under slightly reduced
pressure.
3. Other Methods of Preparation
The only practicable process for the preparation of pentaery-
thritol consists in condensing acetaldehyde with formaldehyde
in dilute aqueous solution by means of calcium (or
56 ORGANIC SYNTHESES
hydroxide; l it has, however, also been formed by the action
of sodium amalgam upon the pentaerythrose produced by con-
densing acetaldehyde with formaldehyde by means of sodium
hydroxide. 2
i Ann. 265, 316 (1891); Ann. 276, 58 (1893); C. A. 11, 2543 (1917); D. R. P.
390,622; Chem. Zcntr. 1924 (i) 2396.
2 Am.Chem. 1.37,38(1907).
XXI
0-PHENYLHYDROXYLAMINE
2Zn+H 2 O -> C G H 5 NHOH + 2ZnO
Prepared by OLIVI R KAMM.
Checked by C S MARVKL.
1. Procedure
IN a 4-gal. earthenware jar are placed 250 g. of technical
ammonium chloride, 8 1. of water, and 500 g. of nitrobenzene.
The mixture is stirred vigorously by means of a mechanical
stirrer, and 020 g. of zinc dust of 85 per cent purity is added
(Note i) during the course of fifteen to twenty minutes (Note
2). As the reduction proceeds, the temperature rises to 6065.
Stirring is continued for fifteen minutes after all the zinc dust
has been added, at the end of which time the reaction is com-
plete, as indicated by the fact that the temperature of the mix-
ture ceases to rise.
While still hot, the solution is filtered with suction in order
to remove the zinc oxide, which is washed with i 1. of hot water.
The filtrate is placed in an enamelled pan, saturated with salt,
about 3 kg. being required, and cooled to o by being placed in
an ice-salt mixture. The phenylhydroxylamine, which crystal-
lizes out in long, light yellow needles (Note 3), is filtered by
suction. The yield of crude product varies considerably,
depending upon the amount of salt solution present, but aver-
ages 350-400 g. This corresponds to 275-300 g. (62-67 P er cent
of the theoretical amount) of actual phenylhydroxylamine, as
determined by its separation from inorganic materials by solu-
tion in ether (Note 4).
Since phenylhydroxylamine deteriorates upon storage, it is
generally used promptly, as illustrated in the preparation of
cupferron, p. 19. The oxalate is somewhat more stable.
57
58 ORGANIC SYNTHESES
2. Notes
1. The zinc dust must be analyzed (Gattermann, " Practical
Methods of Organic Chemistry/' 3rd ed., p. 390), and a propor-
tional quantity used if the zinc content is not 85 per cent.
Technical nitrobenzene is satisfactory if it distils over a range
of not more than 5 degrees and is not acid in reaction.
2. When the reaction is run more slowly, the temperature
does not reach 60-65 and the yield is poorer. At 50-55, the
yield is about 55 per cent.
3. It is important that the phenylhydroxylamine solution be
kept at o for at least one-half hour or considerable material will
be lost in the solution. The use of an enamelled pail saves a
great deal of time at this step.
4. Phenylhydroxylamine is soluble in saturated salt solution
at o to the extent of about 9 grams per liter, but this amount is
not included in the yields given. Occasional yields of 300-
310 g. of dry phenylhydroxylamine have been obtained.
3. Other Methods of Preparation
Although phenylhydroxylamine may be prepared by catalytic
reduction, 1 by the oxidation of aniline, 2 and by electrolytic reduc-
tion of nitrobenzene, 3 the most feasible method is still based
upon the original zinc reduction method of Bamberger 4 and of
Wohl. 5 Various solvents and catalysts have been used in this
reduction, and copper-coated and amalgamated zinc, as well as
aluminium amalgam, 6 have been substituted for zinc dust.
The method herein recommended is essentially one previously
described 7 but it has been found 8 that cooling is not an essential,
as claimed in the patents. The preparation of the oxalate is
also a more recent contribution. 9
1 Ber. 55B, 875 (1922). 2 Ber. 32, 1676 (1899).
3 Chem. Zentr. 1898 (II), 634; Z. physik. Chem. 32, 272 (1900); J. Phys. Chem.
19, 696 (1915).
4 Ber. 27, 1348, 1548 (1894). 6 Ber. 27, 1432 (1894).
6 Beilstein 2*, 241 (1903); J. Chem. Soc. 119, 767 (1921); J. Ind. Eng. Chem.
12, 799 (1920).
7 D R. P. 89,978; Frdl. 4, 47 (1896). 8 J. Am. Chem. Soc. 41, 277 (1919).
9 U. S. Patent 1,390,260; C. A 16, 105 (1922).
XXII
n-PROPYLBENZENE
C 6 H6CH 2 Cl+Mg
C6H 5 CH 2 MgCl+(C 2 H 5 )2SO4 ->
C 6 H 5 CH 2 CH 2 CH 3 +MgCl(SO4C 2 H 5 )
Prepared by HENRY OILMAN and C. H. MEYERS.
Checked by C. S. MARVEL and H. O. CALVERY.
1. Procedure
IN a 5-!. flask standing in an empty water bath are placed
50 g. of clean magnesium turnings and 600 cc. of dry ether
which has been distilled over phosphorus pentoxide and stored
over sodium; the flask is then fitted with a stirrer having a
mercury seal, a thermometer, an efficient reflux condenser, and
a dropping funnel. About 50 cc. of a solution of 253 g. of benzyl
chloride, boiling at 172-175, in 800 cc. of dry ether is then
added through the dropping funnel and the mixture heated just
to boiling by placing in the bath enough water at 40 to cover
about half the surface of that part of the flask which is in con-
tact with the ethereal mixture.
As soon as the ether begins to boil, the warm water is siphoned
out; if the boiling should continue vigorously, owing to the
reaction having set in, the rate may be regulated by placing
cold water in the bath. The remainder of the benzyl chloride
solution is then added at such a rate that the mixture boils
gently; this will require about four hours. When all has been
added, stirring is commenced and the mixture gently boiled for
fifteen minutes by the gradual replacement of the cold water by
warm.
59
60 ORGANIC SYNTHESES
The temperature of the mixture is then lowered by means of
running water, and 385 g. of c. p. ethyl sulfate (Note i) is
dropped in, with continuous stirring, during one and a half
hours, allowing the temperature to rise gradually. When all
has been added, stirring is continued with gentle boiling for an
hour. The cooled mixture is then poured cautiously, with
stirring, upon a mixture of i kg. of crushed ice, i kg. of water,
and 200 cc. of concentrated hydrochloric acid.
After a few minutes, the bulk of the water layer is removed
by a siphon and the clear ethereal solution decanted, so far as
possible, into a 2-1. flask. The remaining mixture is filtered
through a glass-wool plug into a separatory funnel, and after
removal of the aqueous portion, the remaining ethereal solution is
added to that in the flask. An efficient fractionating column
is attached, and the ether distilled on the water bath; the resi-
due is then fractionated and collected as pure w-propylbenzene
boiling at 154-158. The yield is 133-156 g. (55-65 per cent
of the theoretical amount).
2. Notes
i. The technical grade of diethyl sulfate gives poorer yields
on account of the presence of free acid. The c. P. grade was
used in order to obtain the results given in the procedure.
3. Other Methods of Preparation
w-Propylbenzene has been prepared by the action of sodium
on a mixture of propyl bromide and bromobenzene, 1 of zinc
dust upon a benzene solution of allyl bromide, 2 and of zinc ethyl
upon benzyl chloride; 3 and aluminium chloride has been
employed to condense benzene with propyl bromide, 4 allyl
'Ann. 149, 324(1869).
2 Jahresb. 1806, 1516; Bull. soc. chim. (3) 16, 126 (1896).
3 Ber. 10, 294 (1877); Gazz. chim. ital. 7, 21 (1877).
4 Ber. 24, 768 (1891); J. Russ. Phys. Chem. Soc. 27, 457 (1895); Bull. soc.
chim. (3) 16, 864 (1896).
w-PROPYLBENZENE 61
chloride 5 and trimethylene bromide, 6 but the tendency of this
reagent to induce isomerization is a distinct danger.
tt-Propylbenzene has also been obtained by the action of hot
sulfuric acid upon a mixture of propyl alcohol and benzene. 7
Reduction methods have been applied to various monosub-
stituted benzene derivatives possessing a three-carbon-chain,
namely, phenyl ethyl ketone and benzyl methyl ketone, 8
7-phenyl ;z-propyl chloride or bromide, 9 propenylbenzene, 10
phenyl ethyl ketoxime n and cinnamyl alcohol or phenyl allyl
alcohol. 12
5 Ann. 218, 379 (188.3); Bull soc. chim. (2) 41, 197 (1884); (2) 43, 588 (1885).
6 Compt. rend. 132, 155 (IQOI)
7 Compt rend 117, 236 (1893).
8 J. prakt. Chem (2) 81, ^87 (IQTO); Rer 40, 1830 (1013).
Ber 43, 178 (IQIO), 44, 2872 (IQII); 45, 2176, 2179 (1912).
10 Ber. 36, 622, 773 (1903)
11 Bull. soc. chim. (4) 9, 465 (1911).
12 Ber. 39, 2590 (1906).
XXIII
PYRUVIC ACID
CHOHCOaH
| +(KHSO 4 )
CHOHCO 2 H
Prepared by J. W. HOWARD and W A FRASER.
Checked by C S MARVEL and R L SHRINER.
1. Procedure
AN intimate mixture of 600 g. of finely powdered freshly
fused potassium acid sulfate and 400 g. of powdered tartaric acid,
prepared by grinding them together in a mortar, is placed in a
3-1. round-bottom Pyrex flask connected with a condenser which
is rilled with water but does not have any water flowing through
it. The mixture is heated by means of an oil bath maintained
at a temperature between 210 and 220 until liquid no longer
distils over. Some foaming takes place (Note i), but if fused
potassium acid sulfate is used and the temperature of the bath
does not rise above 220, it is not difficult to control. The dis-
tillate is then fractionated under reduced pressure. Pyruvic
acid passes over at 75-80; 25 mm. and the yield is 117-128 g.
(50-55 per cent of the theoretical amount).
2. Notes
1. If the mixture foams badly, it may be kept from frothing
over by heating the upper part of the flask with a free flame.
2. The cake left in the reaction flask may be removed readily
by inverting over a steam jet.
3. Other Methods of Preparation
Pyruvic acid has been prepared from ,a-dichloropropionic
acid and from the corresponding dibromo acid, by heating with
63
G4 ORGANIC SYNTHESES
water under pressure, by heating with barium hydroxide solu-
tion, and by the treatment of the aqueous solutions with silver
oxide or silver carbonate. 1 The action of sodium hydroxide on
a,a-dibromopropionic acid has also been studied. 2 Better
results have been reported from the hydrolysis of acetyl cyanide
and of oxalacetic ester. 3
It has been obtained by the oxidation of lactic acid, 4 mesa-
conic acid and citraconic acid, 5 acetone and acetol, 6 but in
general these oxidation procedures are not suitable as prepara-
tive methods.
Pyruvic acid may be obtained by the distillation of tartaric
acid or gly eerie acid. 7 Better results are obtained, however, by
the distillation of tartaric acid in the presence of a dehydrating
agent such as potassium bisulfate. 8 This method has been
adopted after a study of a variety of dehydrating agents and
various experimental procedures.
1 Ber. 5, 477 (1872), 10, 264, 2037 (187?), 18, 228, 235 (1885).
2 Ann. 342, 132 (1905).
3 Ber. 11, 620, 156.3 (1878), Ann. 240, 327 (1888).
4 J. Chem. Soc 77, 71 (1900); Ber. 17, 840 (1884); Chem. Met Eng 28, 357
(1923).
5 Ann. 305, 48, 49 (1899).
6 Compt rend. 140, 1592 (1905), Bull soc. chirn. (4) 3, 250 (1908); Ber. 20,
641 (1887); J. Am Chem Soc 3, 2661 (1917).
7 Ann physik (2)30,1(1835), Ann 131,338(1864), 188,314(1877).
8 Ber. 14, 321 (1881); Bull, soc chim (3)13,335(1895), Rec trav. chirn. 19,
278 (1900), Ann. 242, 269 (1887); Ber. 43, 2188 (1910).
XXIV
SODIUM />-HYDROXYPHENYLARSONATE
Prepared by W G CHRISTIANSEN and A. J. NORTON.
Checked by OLIVER KAMM.
1. Procedure
SEVEN HUNDRED AND TWENTY grams of syrupy arsenic acid
(75-80 per cent) is boiled in a beaker until the temperature of
the acid is 150; about 120 g. of water is driven off, leaving a
syrup containing approximately 95 per cent of orthoarsenic
acid, which is then added to 300 g. of phenol in a i-l. round-
bottom, short-neck Fyrex flask. By means of a 3-hole stopper,
an efficient jacketed stirrer (Org. Syn. i, 4) and a thermometer
are introduced into the flask, and a connection is established
with a downward condenser. The flask is set in an oil bath
which is heated at once to 155-160, and the stirrer is run at a
rate high enough to insure thorough mixing.
When the inside temperature reaches 140, boiling com-
mences and water plus a very little phenol begins to distil.
The distillation is allowed to continue until 60 cc. (one molecular
equivalent) of water has been collected; this usually requires
one hour, and the inside temperature rises to 146. The down-
ward condenser is then replaced by a reflux condenser (Note i)
and the reaction is allowed to continue until a total of four
hours has elapsed from the time the contents of the flask first
reached 140. After the return condenser has been attached,
the inside temperature declines slowly to 141 or 142 and the
reaction mixture becomes thicker and somewhat tarry. After
the contents of the flask have been partially cooled, they are
65
66 . ORGANIC SYNTHESES
*
poured into 4 1. of water and mechanically stirred; the agitation
is continued for a short time in order to break up the tarry
material and enable the water to dissolve the hydroxyphenyl-
arsonic acids completely.
Finely ground barium hydroxide is added gradually to the
well-stirred water solution until the material is slightly alkaline
to litmus, in prder to remove the excess of arsenic acid; when
this point is reached, the solution becomes pink. If the pro-
cedure is carried out properly, 700-800 g. of Ba(OH) 2 8H2O
should suffice (Note 2). The time required by this method is
greater than when a hot solution of barium hydroxide is used,
but the method is more convenient and does not cause such a
great increase in volume. After removal of the barium arsenate
by filtration, the mother liquor and washings are treated with
sulfuric acid until the solution contains neither barium nor
sulfate ions. When the barium sulfate has been separated and
thoroughly washed (Note 3), the filtrate is concentrated on a
steam bath to about 3 1., neutralized to litmus with sodium
hydroxide, filtered, evaporated until the solution becomes well
coated with crystals, and then treated with 2.5 volumes of alcohol.
After the mixture has cooled in an ice-box, the sodium />-hydroxy-
phenylarsonate is separated, washed with alcohol, and dried in
an oven at 80. A second crop may be secured from the filtrate
by concentrating it further and precipitating with alcohol.
The total yield of anhydrous sodium />-hydroxyphenylarsonate
is 252 g. (33 per cent of the theoretical amount). By proper
manipulation, it is possible to obtain as much as 240 g. in the
first crop and to have it free from sulfate, arsenate, and sodium
0-hydroxyphenylarsonate which is one of the by-products formed
in this reaction (Note 4).
2. Notes
i. When the downward condenser is not replaced by a reflux
condenser, the total volume of water that distils is 90-120 cc.
and the mass becomes very tarry, owing to the oxidation of
phenol or of some intermediate substance formed in the reaction.
SODIUM />-HYDROXYPHENYLARSONATE 67
/>-Hydroxyphenylarsonic acid is not destructively oxidized by
hot arsenic acid.
2. In removing the excess arsenic acid with barium hydroxide,
the solution should not be permitted to become strongly alka-
line, as the barium salt of the hydroxyphenylar sonic acid may
commence to separate, thereby decreasing the yield.
3. The filtration of large quantities of barium sulfate is
usually tedious; but if filtering carbon is added to the suspension
to be filtered and if a mat of this carbon is prepared on the filter
by filtering an aqueous suspension of carbon, the barium sulfate
may be removed rapidly and completely, even when it is pre-
cipitated from cold solutions.
4. When phenol is arsonated with arsenic acid, small amounts
of 0-hydroxyphenylarsonic acid, /?,//-di-hydroxyphenylarsinic
acid and 0,//-di-hydroxyphenylarsinic acid are formed as by-
products. As the sodium salts of the secondary acids are soluble
in alcohol, they will not appear in the material precipitated by
the addition of alcohol. The sodium salt of 0-hydroxyphenyl-
arsonic acid, although insoluble in alcohol, will not be precipi-
tated if the solution is not concentrated too far before addition
of the alcohol. To test the material for the presence of the
ortho compound, ferric chloride is added to an aqueous solution
of a small amount of the solid; the ortho hydroxy acid gives a
deep purple color, whereas the para acid gives no coloration.
The sodium salt which is precipitated with alcohol contains
water of crystallization, which is driven off by drying at 80.
The product can be purified by dissolving in hot water and adding
hot alcohol until a slight permanent turbidity is produced.
Upon cooling, the material separates in a crystalline condition.
Occasionally, the second crops of sodium />-hydroxyphenyl-
arsonate contain small amounts of arsenious oxide which is
formed from the arsenic acid during the oxidation mentioned
above.
3. Other Methods of Preparation
/>-Hydroxyphenylarsonic acid may be prepared by diazotiza-
tion of arsanilic acid and replacement of the diazo group by
68 ORGANIC SYNTHESES
*
hydroxyl. 1 The method of directly introducing the arsenic
acid group into phenol is more satisfactory. This preparation
was first described in the patent literature, 2 but the method
proved unworkable and was reinvestigated and improved by
Conant 3 and later by Jacobs and Heidelberger. 4 In the present
method, 5 additional improvements have been effected.
!Ber. 41, 1854 (iqo8).
2 D. R. P. 205,616; Frdl. 9, 1040 (igo8).
3 J. Am. Chem. Soc. 41, 431 (IQIQ)
4 J. Am. Chem. Soc. 41, 1440 (IQIQ).
5 J. Am. Chem. Soc. 45, 2188 (1923).
XXV
o-TOLUNITRILE AND />TOLUNITRILE
CH 3 C ti H 4 NH 2 +HN0 2 +HCl
CH 3 C6H 4 N2Cl+NaOH+NaCu(CN)2 ->
CH 3 C G H 4 CN+N2+NaCl + CuCN
Prepared by H. T CLXRKK and R. R. READ.
Checked by C S. MARVEL and M. M BRUBAKER.
1. Procedure
A. Preparation of the cuprous cyanide solution: Cuprous
chloride prepared from 1250 g. of copper sulfate, according to
the directions given in Org. Syn. 3, 33, is suspended in 2 1. of
cold water in a 15-!. crock fitted with a mechanical stirrer. A
solution of 050 g. of sodium cyanide (96-98 per cent) in i 1. of
water is added and the mixture stirred, whereupon the cuprous
chloride enters into solution with considerable evolution of heat
(Note i). The mixture is then cooled by surrounding the crock
with cold water (Note 2).
B. Preparation of o-tolunilrilc: While the cuprous cyanide
solution is cooling, 428 g. of 0-toluidinc is mixed in a 20-!. crock
with T 1. of commercial 28 per cent hydrochloric acid (sp. gr.
1.14) and enough cracked ice, about 4 kg., to bring the tempera-
ture of the mixture to o. A solution of 280 g. of sodium nitrite
in 800 cc. of water is added, with stirring, to the resulting suspen-
sion of 0-toluidine hydrochloride, the temperature being kept at
05 by the addition of cracked ice. The addition of the nitrite
occupies about fifteen minutes; at the end of the operation, the
mixture must show a distinct and permanent reaction for free
nitrous acid on testing with starch iodide paper (Note 3). The
final volume of the solution is 5-6 1. The mixture is now
69
70 ORGANIC SYNTHESES
cautiously neutralized by adding dry sodium carbonate with
constant stirring, using litmus paper to determine the end point;
about 200 g. of the anhydrous carbonate is required (Note 4).
The cold cuprous cyanide solution is now chilled to 0-5 by
the addition of ice, and i 1. of benzene is poured on the surface.
To this mixture is slowly added the cold neutralized diazonium
solution. During the addition, which occupies about thirty
minutes, such vigorous stirring is maintained that the benzene
on the surface is constantly drawn to the stirrer, and the tempera-
ture is maintained at 0-5 by occasionally adding ice. As soon
as the diazonium solution comes into contact with the cuprous
cyanide, a dark yellow, oily precipitate is formed which at once
begins to give off nitrogen; the resulting nitrile is taken up by
the benzene as soon as it is formed (Note 5). When all has
been added, the temperature is held at 0-5 for thirty minutes
longer, and then is allowed to rise to that of the room (20-25),
which usually requires about three hours.
After stirring has been continued for two hours longer, the
crock is surrounded by hot water or steam and warmed to 50
without stirring. The mixture is then allowed to stand until
cool, when the aqueous layer is drawn off by means of a siphon.
The upper oily layer is transferred to a 12-!. flask and distilled
in a current of steam until no more oil passes over; about 10 1.
of distillate is collected (Note 6). The water is drawn off and
the benzene removed by distillation, by means of a 2-1. round-
bottom flask and a fractionating column about 90 cm. long.
When benzene no longer distils over, the distillation is continued
in the same apparatus under reduced pressure, and the fraction
that boils at g4~g6/2o mm. is collected. A small amount of
dark-colored residue remains in the flask. The yield of almost
colorless 0-tolunitrile is 300-330 g. (64-70 per cent of the theo-
retical amount).
^-Tolunitrile can be prepared in exactly the same manner
from />-toluidine; the product, which distils at I04-io6/2o mm.,
solidifies in the receiver to a mass of nearly colorless needles
which melt at 25-27. The yield is the same as with the ortho
compound (Note 7).
o-TOLUNITRILE AND />-TOLUNITRILE 71
2, Notes
1. If desired, the cuprous chloride may be suspended in 3 1.
of water and the sodium cyanide added in the solid form.
2. If several runs are to be made it may be more convenient
to prepare a large quantity of cuprous cyanide solution, since
this appears to be stable for several days.
3. If the sodium nitrite is not of the highest technical purity
it may be necessary to employ more than the indicated quantity.
It is essential that the test for nitrous acid be permanent; if
any unchanged amine remains, a precipitate of the diazoamino
compound is formed on neutralization. A moderate excess of
nitrite does not appear to interfere with the reaction, especially
since the greater portion of the free nitrous acid is removed by
the carbon dioxide liberated on neutralization.
4. Sodium carbonate is preferable to sodium hydroxide
because very little heat is evolved on neutralization. A slight
excess of carbonate does not appear to be harmful.
5. It is essential that the stirring be very vigorous. If the
intermediate addition compound is allowed to collect on the
surface of the liquid, it decomposes spontaneously with evolu-
tion of much heat; this decomposition may take place with
almost explosive violence. The presence of the benzene tends
to diminish the viscosity of the intermediate product and permit
it to be readily distributed throughout the mixture. Decom-
position is quite rapid at o and is practically complete when
room temperature is reached; it appears, however, to be advis-
able to warm the mixture to 50, since if this be omitted the
yield is slightly decreased.
6. The apparatus described in Org. Syn. 2, 80, is suitable for
the steam distillation.
7. The product, as obtained in the above procedure, is of
high purity; cresols do not appear to be formed under the con-
ditions specified. The process has the advantage over that
described in the literature l of giving rise to no poisonous fumes
during the formation of the cuprous cyanide and during the
interaction of this with the diazonium salt. The yield is prac-
tically the same as in the older method.
72 ORGANIC SYNTHESES
3. Other Methods of Preparation
The original method of Sandmeyer l prescribed the prepara-
tion of the cuprous cyanide solution by dissolving copper sulfate
in potassium cyanide solution and adding the strongly acid
diazonium solution to it. Both of these operations involve the
evolution of poisonous gases cyanogen in the first case and
hydrogen cyanide in the second. Slight modifications have
been subsequently suggested : the use of a 50 per cent excess of
cuprous cyanide 2 and the heating of the cuprous cyanide solu-
tion before the reaction. 3
0-Tolunitrile has also been prepared from 0-toluidine by
conversion into 0-tolyl isolhiocyanate and the boiling of this
under a reflux condenser; 4 /?-tolunitrile has been prepared by
distilling /?-toluic acid with potassium thiocyanate; 3 and a
mixture of the two has been produced by the interaction of
toluene, mercury fulminate, and aluminium chloride. 6
1 Ber. 17, 2653 (1884); 18, 1492, 1496 (1885).
2 Bcr. 19, 756 (1886).
3 Ber. 23, 1026 (1890).
4 Ber. 6, 419(1873).
5 Ber 8,441 (1875).
6 Ber. 36, 14 (1903).
XXVI
7>TOLUYL-o-BENZOIC ACID
A1 2 C1,0
Prepared by L F. FIKSER.
Checked by ROGER ADAMS and R. L. SHRIXER.
1. Procedure
A 2-1. round-bottom flask is clamped to a ring-stand and
equipped with a rubber stopper protected with tin foil and car-
rying a glass stirrer with mercury seal and a reflux condenser.
(Cf. Org. Syn. i, 4, Fig. i, a.) As an outlet for the hydrogen
chloride, the top of the condenser is provided with a bent tube
which almost touches the surface of the water in a half-rilled
i-l. flask.
One hundred grams of phthalic anhydride and 400 g. of
toluene are placed in the flask, which is cooled in an ice bath
while 200 g. of anhydrous aluminium chloride (Note i) is being
ground to a fine powder. The chloride is now added all at once,
and connections to the condenser made as rapidly as possible.
Stirring is commenced at once and the ice bath is removed.
The mixture warms up considerably and becomes olive-green
in color. When the evolution of hydrogen chloride begins to
slacken (ten minutes) a water bath is put into place and heated
to 90 in the course of forty-five minutes. The temperature of
the bath is kept at 90 and vigorous stirring continued for two
and one-half hours. At this point, the evolution of hydrogen
chloride will have practically ceased and the reaction will have
been completed. The hot water in the bath is replaced first by
cold water and then by ice, while stirring is continued.
73
74 ORGANIC SYNTHESES
As soon as the flask is well cooled, it is disconnected and
carried to the hood, and ice is slowly added, with shaking, until
the dark mass is completely decomposed and the flask is about
half filled with the mixture. After 150 cc. of crude concentrated
hydrochloric acid has been added, the mass coagulates and the
solution clears; the flask is then heated on the steam bath while
preparations are being made for steam distillation.
This operation, which removes the excess of toluene, may be
carried out in the same flask and loss by transfer thus avoided
(Note 2). The aqueous solution of aluminium chloride and
hydrochloric acid, after thorough cooling, is decanted through a
suction filter, the residue washed with a little cold water, and
that collected on the filter returned to the flask. This residue
consists almost solely of toluylbenzoic acid, partly crystalline,
partly in oily lumps.
A previously prepared and heated solution of 50 g. of sodium
carbonate in i 1. of water is added, and steam is passed in to
provide heat and agitation. With a rapid stream, the acid will
go into solution in about ten minutes, leaving a small amount
of brown, tarry material and a little alumina undissolved
(Note 3). The solution is filtered while hot and transferred to a
2-1. beaker, and the acid precipitated by the addition of 65 cc.
of concentrated hydrochloric acid. The acid separates as an
oil, which soon crystallizes. The solution is cooled in ice and
the acid filtered and washed.
The air-dried product is pure white and weighs 170 g. (Note 4).
After drying at 100, the anhydrous acid melts at 138-139 and
weighs 157 g. (96 per cent of the theoretical amount). Air-dried
material is suitable for the condensation to ^-methyl anthra-
quinone, p. 43. It may be recrystallized from toluene.
2. Notes
i. Although statements are found in the literature that
quantitative yields may be obtained with smaller quantities of
aluminium chloride, the ratio iCsH^CO^O : iAl 2 Clo is essen-
tial.
^-TOLUYL-o-BENZOIC ACID 75
2. The steam distillation requires about fifteen minutes, and
about 340-380 cc. of toluene is recovered.
3. If, in extracting the acid with sodium carbonate, more
than 2-3 g. of material remains undissolved, the residue is treated
with dilute hydrochloric acid to remove alumina, washed, and
again extracted with a little carbonate solution. This extract
is neutralized separately since some tar may separate with the
toluyl benzoic acid. In this event, it is filtered and extracted
with cold carbonate solution, in which the tar is completely
insoluble.
4. According to Limpricht, the acid may Crystallize either
in hydra ted or in the anhydrous condition, but the transition
temperature is not stated. The loss of water upon drying at
100 shows the compound obtained in this experiment to be the
monohydrate.
3. Other Methods of Preparation
The only practical method for the preparation of ^-toluyl-
0-benzoic acid is that proposed by Friedel and Crafts. 1 Limp-
richt 2 has proposed a decrease in the quantity of aluminium
chloride, but Heller and Schulke 3 and McMullen 4 have verified
the importance of an excess of the condensing agent.
1 Ann. chim. phys. (6) 14, 447 (1888).
2 Ann. 299, 300 (1898;.
3 Ber. 41, 3632 (1908).
4 J Am Chem. Soc. 43, 1965 (1921).
XXVII
TRICARBALLYLIC ACID
Prepared by H. T. CLARKE and T. F. MURRAY.
Checked by C. S. MARVEL and M. M. BRUBAKER.
1. Procedure
IN a 3-1. flask, fitted with a stirrer and a fractionating column
with condenser for downward distillation, are placed 912 g. of
ethyl propane-i,i,2,3-tetracarboxylate (p. 29) and 950 cc. of a
solution of equal volumes of pure concentrated hydrochloric acid
and distilled water. A receiver with a side-tube is attached to
the condenser; this side-tube leads to a water trap. The mix-
ture is boiled, with continual stirring, at such a rate that the
alcohol is removed as fast as it is formed, but without undue
removal of water from the flask (Note i). The progress of the
reaction can be followed by noting the rate at which carbon
dioxide passes through the trap. When the temperature at the
head of the column approaches 100, the flame is turned down
so that very little liquid distils over. Heating is continued until
evolution of carbon dioxide ceases (Note 2) .
The flask is now disconnected from the stirrer and column,
and the contents distilled off as completely as possible on the
steam bath under reduced pressure. The remaining solid is
freed from residual moisture and hydrochloric acid by allowing
a slow current of dry air to pass over it, while still heating on the
steam bath and maintaining a partial vacuum (Note 3). It is
then redissolved in distilled water, and the solution filtered with
77
78 ORGANIC SYNTHESES
the use of decolorizing carbon, and again evaporated under
reduced pressure.
The residue, when completely dry, is ground up, mixed to a
paste with dry ether, filtered by suction, washed with dry ether
and dried. The product so obtained (Note 4) is practically
pure and melts at 160-161. The yield is 474-479 g. (95-96 per
cent of the theoretical amount).
2. Notes
1. The temperature at the head of the column will give some
idea of the relative amount of water passing over with the
alcohol, but allowance must be made for the lowering of the
distilling temperature by the carbon dioxide evolved.
2. Twelve hours' heating is necessary to complete the reac-
tion.
3. The dry air is best introduced through a tube leading to
the bottom of the flask; it is well not to disconnect the con-
denser, but to note the point at which no more drops condense.
The current of dry air should be quite slow not more than two
bubbles per second in the sulfuric acid wash bottle.
4. Tricarballylic acid is readily soluble in water (requiring
about twice its weight at room temperature), but may, if
desired, be recrystallized from it. Dry ether may also be
employed, about 50 parts by weight being necessary.
3. Other Methods of Preparation
Tricarballylic acid was originally prepared by hydrolysis of
the nitrile obtained from glycerol tribromohydrin and potassium
cyanide; l it has also been obtained by the reduction of aconitic
acid by sodium amalgam 2 or electrolytically. 3 The hydrolysis
of ethyl propanetetracarboxylate may be carried out either in
acid solution (with hydrochloric acid) 4 or in alkaline solution, 5
1 Proc. Roy. Soc. 12, 237 (1862); Ann. 128, 352 (1863); Ann. 136, 272 (1865).
2 Ann. 132, 62 (1864); Ber. 22, 2920 (1889); Ann. 314, 15 (1901).
3 Compt. rend. 136, 1331 (1903).
4 Ber. 24, 2889 (1891); Ann. 341, 102 (1905;.
6 Ber. 23, 3760 (1890); J. prakt. Chem. (2) 45, 56 (1892).
TRICARBALLYLIC ACID 79
the former being the more convenient. Tricarballylic acid is
also formed by the acid hydrolysis of the less accessible methyl
propanepentacarboxylate and methyl propanehexacarboxylate, 7
as well as by the alkaline hydrolysis of acetyl tricarballylic ester. 8
Finally, it has been obtained by the oxidation of dkllylacetic
ester with nitric acid 9 and of gallic acid with potassium chlorate
and hydrochloric acid. 10
Ber, 29, 1742 (1896); Ann. 347, 7 (1906).
7 Ber. 29, 1279 (1896).
8 Ann. 190, 324 (1878); Ber. 23, 3756 (1890).
9 Ann. 201, 53 (1880).
10 Ann. 177, 292 (1875).
XXVIII
TRIPHENYLMETHANE
Alds - (C 6 H 5 ) 3 Ca-AlCl 3 +3HCl
(C6H 5 ) 3 CC1-A1C1 3 +(C 2 H5) 2 -
(C ri H 5 ) 3 CH+ CH 3 CHO + C 2 Hr,Cl + A1C1 3
Prepared by J. F. NORRIS.
Checked by H. T. CLARKE and T. F. MURRAY.
1. Procedure
To a mixture of 292 g. of dry benzene and 116 g. of dry
carbon tetrachloride, (Note i) in a i-l. flask provided with a
reflux condenser having a calcium chloride tube at its upper end,
is added 100 g. of anhydrous aluminium chloride in lumps
(Note 2). The flask is at once immersed in ice-water to within
5 cm. of the top, and allowed to stand for twenty-four hours,
the temperature of the water being allowed to rise to that of the
room (Note 3). One hundred and ten grams of anhydrous ether
is added in small portions, through the condenser, the flask being
shaken occasionally during twenty minutes. The mixture is
allowed to stand for twenty-four hours, and is then poured into
a 5-!. flask containing 650 g. of ice and 25 cc. of concentrated
hydrochloric acid. One liter of benzene is then added, and the
mixture heated on a steam bath under a return condenser.
After gently boiling for five to ten minutes, the mixture is allowed
to cool to 40-50, when the benzene layer is separated, washed
with 700 cc. of warm water containing 25 cc. of concentrated
hydrochloric acid, and distilled. After the benzene has been
removed under atmospheric pressure, the residue is transferred
to a 300-cc. flask and distilled under reduced pressure, and a
81
82 ORGANIC SYNTHESES
fraction boiling over the range 190-2 is/io mm. collected
(Note 4). This weighs 135-160 g.; it solidifies on cooling. It
is recrystallized from 550-650 cc. of ethyl alcohol (Note 5), and
a colorless product, crystallizing in needles which melt sharply
at 92, is obtained. This is filtered off and washed twice with
3o-cc. portions of fresh alcohol. The alcoholic mother liquor is
concentrated and the residue distilled under reduced pressure,
material which distils over at i9o-2oo/io mm. being collected.
This is recrystallized from ethyl alcohol, and 6-7 g. more of
pure material is thus obtained. The total yield is 125-154 g.
(68-84 per cent of the theoretical amount).
2. Notes
1. A convenient method for removing moisture from the
carbon tetrachloride and the benzene consists in distilling off
about one-tenth of the liquid; this first fraction contains all the
moisture which may have been dissolved in the commercial
products. It is, as a rule, unnecessary to distil the remaining
liquid before use.
2. The aluminium chloride may be a good grade of technical
anhydrous material. If a powdered product be employed, the
reaction is apt to proceed too rapidly. The lump material
appears to be somewhat more efficient.
3. With shorter periods of standing and lower temperatures,
the yield falls off materially. Thus in one experiment in which
the mixture was allowed to stand for twenty-four hours at 5-8,
a large proportion of a lower-boiling product (apparently
diphenylmethane) was formed, and only 109 g. of crude tri-
phenylmethane was obtained.
4. A dark, tarry residue amounting to 25-40 g. remains in
the flask.
5. Methyl alcohol may also be employed, but it is necessary
to use 1600-1700 cc. of it. Triphenylmethane dissolves in one-
third of its weight of warm benzene; it separates from this
solution with benzene of crystallization, which is lost on exposure
to air or recrystallization from alcohol.
TRIPHENYLMETHANE 83
3. Other Methods of Preparation
The process here described consists essentially in the forma-
tion of triphenylchloromethane by the interaction of carbon
tetrachloride and benzene in the presence of aluminium chloride,
and the reduction of this product by ether under the influence
of the aluminium chloride present.
Triphenylchloromethane is most satisfactorily prepared by
the above method, 1 though ferric chloride may also be employed
as a catalyst. 2 Its reduction by means of ether was first
observed by Gomberg, 3 the catalyst in this case being zinc
chloride; it had previously been shown 4 that triphenylchloro-
methane (or triphenylcarbinol) is reduced to triphenylmethane
by means of alcohol in the presence of sulfuric acid.
Triphenylmethane has hitherto usually been prepared by
the interaction of benzene and chloroform in the presence of
aluminium chloride 5 or ferric chloride, 2 but the yields are con-
siderably lower. Other methods consist in the action of benzal
chloride upon benzene and aluminium chloride, 6 in heating
benzal chloride and mercury diphenyl, 7 and in heating a mixture
of benzaldehyde, benzene, and zinc chloride. 8
ifier. 33, 3147 (1900).
2 Ber. 32, 2422 (1899).
3 J. Amer. Chem. Soc. 35, 204 (1913;.
4 Ber. 45, 3188 (1912).
5 Ber. 14, 1516 (1881); 26, 19^1 (1893); Bull. soc. chim. (2) 37, 6 (1882);
Ann. 227, 108 (1885).
6 Am Chem. J. 13, 556 (1891).
7 Ber. 5, 906 (1872).
s Ann. 242, 329 (1887).
INDEX
Absolute alcohol, IV, n, 29. (See also
Ethyl alcohol.)
Acetal, III, 1-2
Acetaldehyde, III, i, gi, 92; IV, 53
Acetamide, III, 3-5
Acetanilide, IV, 40
Acetic acid, II, 18, 33, 64; III, 3, n,
455 IV, 5, 47
Acetic anhydride, III, 21; IV, 35
Acetone, I, 45-47, 53, 54, II, 41; HI,
17,58,61; IV, 39
Acetophenone, II, i
Acetoxime, III, 62
Acetylation, IV, i, 35, 40
Acetyl chloride, IV, i
Acetylene, IV, 23
Acetyl mandelyl chloride, IV, 1-2
Alkali fusion, III, 37
Alkyl bromides, I, 1-13
Alkylene bromides, I, i, 8, 9
Allyl alcohol, I, 3, n, 15-19
Allyl bromide, I, i, 3, n, 17
Aluminium chloride, IV, 73, 8 1
a-Aminocaproic acid, IV, 3-4
i, 4-Aminonaphthol hydrochloride, III,
7-10
^-Aminophenylacetic acid, III, 11-12
Ammonia, IV, 19
Ammonium carbonate, II, 75; III, 3, 4;
IV, 20
Ammonium chloride, I, 75, 79, 81; III,
67; IV, 47, 57
Ammonium hydroxide, II, 37, 75; III,
; IV, 3
Ammonium sulfide, III, n
iso-Amyl alcohol, I, 4, 10
tso-Amyl bromide, I, i, 2, 4-5, 10
Aniline, II, 71, 79; III, 7, 13; IV, 40
Aniline arsenate, III, 13
Aniline hydrochloride, III, 95
Anthranilic acid, II, 47
Arsanilic acid, III, 13-16
Arsenation, IV, 5
direct, III, 13; IV, 65
Arsenic acid, III, 13, 14; IV, 65
Arsenious oxide, IV, 5, 27
Arsenoacetic acid, IV, 5-7
Arsonoacetic acid, IV, 5-7
B
Barium arsonoacetate, IV, 5
Barium chloride, IV, 5
Barium hydroxide, I, 45, 46; IV, 66
Benzalacetone, III, 17-19
Benzalacetophenone, II, 1-3
Benzaldehyde, I, 33; II, i, 5; III, 17
Benzene, IV, 81
Benzeneazo-a-naphthol, III, 8
Benzenediazonium chloride, III, 7
Benzenesulfonyl chloride, I, 21-23,
7i, 72,81
Benzil, I, 25- 27, 29, 30
Benzilic acid, I, 29-32; III, 45
Benzoic acid, I, 30; II, 5; III, 21
Benzoic anhydride, III, 21-24
Benzoin, I, 25, 26, 33-34
Benzoquinone, II, 85-88; IV, 35
Benzoyl acetate, III, 22
Benzyl alcohol, II, 5
Benzyl benzoate, II, 5-8
Benzyl chloride, II, 9; IV, 59
Benzyl cyanide, II, 9-11, 27, 57, 63
Borax, IV, 46
Bromine, I, 2, 3, 35, 39; III, 41; IV, 9
Bromine in glycerol, IV, 14, 38
86
INDEX
a-Bromo-w-caproic acid, IV, 3, 9-10
<x-Bromonaphthalene, I, 35-37
0-Bromophenol, I, 40, 41
/>-Bromophenol, I, 39-43
0-Bromopropionic acid, III, 25-26, 51
Bromostyrene, II, 67
n-Butyl alcohol, I, 5, 6; III, 69
w-Butyl bromide, I, 2, 5-6, 10; IV, n
-Butylmalonic ester (ethyl), IV, 11-12
n-Butyl nitrite, IV, 19-20
C
Calcium chloride, III, i, 34, 84, 92
Calcium oxide, IV, 53
Calomel, III, 100
w-Caproic acid, IV, 9
Capryl alcohol. (See Methyl hexyl car-
binol.)
Carbanilide, III, 95
Carbon disulfide, I, 39, 41
Carbontetrachloride, I, 17, 67-70; II,
23; III, 25, 41, 51, 76; IV, 29, 81
Castor oil, I, 61, 63, 65
Catechol, III, 27-82
Chlorine, II, 37
Chloroacetic acid, III, 53, 83; IV, 5
Chlorobenzene, I, 21
Chloroform, I, 81; 111,68; IV, 37
0-Chloromercuriphenol, IV, 13-14, 37
/>-Chloromercuriphenol, IV, 13
0-Chlorotoluene, III, 33-35
/>-Chlorotoluene, III, 34
Congo Red, III, 15, 61
Copper sulfate, II, 38; III, 33, 79
Corn cobs, I, 49, 51
Coupling Reaction, II, 47; III, 7
Creatine, IV, 15
Creatinine, IV, 15-17
Creatinine picrate, IV, 16
Creatinine zinc chloride, IV, 15
/>-Cresol, III, 37-39
Cupferron, IV, 19-21
Cuprous chloride, III, 33, 34, 79; IV, 69
Cuprous cyanide, IV, 69
D
Decarboxylation, II, 93
Dehydration, I, 53, 67; III, 3, 21; IV,
IS
Diacetone alcohol, I, 45-47, 53, 54
Diagrams :
Acetylene condensation, IV, 24
Automatic extraction, III, 88
Automatic separation, I, 64, 68;
II, 23; III, 29
Concentration of liquids, IV, 54
Condensation of low-boiling liquids, I,
76
Dehydration with solvent, II, 23
Distillation flask and column, I, 40
Extraction and crystallization, II, 49;
III, 88
Hopper, III, 47
Manipulation of gases, IV, 24
Mechanical stirrcr, I, 4, 12; III, 29
Mercury seal, I, 4
Pyrogenic decomposition, IV, 40
Rapid evaporation, IV, 54
Steam distillations, I, 50; II, 80
Diazotization, II, 47, 71, 80; III, 7, 9,
33, 79,87,89; IV, 69
Dibenzalacetone, III, 18
Dibenzyl ether, II, 6
9, lo-Dibromoanthracene, III, 41-43
1, 4-Dibromonaphthalene, I, 35, 36
2, 4-Dibromophenol, T, 40
a, 7-Dichloroacetone, II, 13-15
Diethyl malonate, IV, n, 27, 29
Dihydroxymethylbenzopyrone. (See /3-
Methyl esculetin.)
Dimethylamine hydrochloride, I, 81;
III, 68
/>-Dimethylaminobenzaldehycie, II, 17-
21
Dimethylaniline, II, 17, 47
Diphenylacetic acid, III, 45-46
Diphenylurea, III, 95
Disodium phosphate, IV, 50
Di-/>-tolylethane (unsym), IV, 23-25
E
Epichlorohydrin, III, 47-49
Esterification, III, 51, 53; II, 23, 27
Ether. (See Ethyl ether )
Ethyl acetate, III, 96
Ethyl acetoacetate, IV, 45
INDEX
Ethyl alcohol, 1, 6; II, 23, 27; III, 1,51,
54, 68, 69, 91; IV, n, 29
Ethyl bromide, I, i, 6-7
Ethyl /3-bromopropionate, III, 51-52
Ethyl cyanoacetate, III, 53-56
Ethylene chlorohydrin, III, 57
Ethyl ether, III, 47, 48; IV, 59, 81
Ethyl fumarate, IV, 29
Ethyl hydracrylate, III, 52
Ethyl malonate, IV, n, 27, 29
Ethyl mesoxalate, IV, 27
Ethyl oxalate, II, 23-26
Ethyl oxomalonate, IV, 27 -28
Ethyl phcnylacetate, II, 27-28
Ethyl propanc-i, i, 2, 3-tetracarboxyl-
ate, IV, 29 30, 77
Ethyl sulfate, IV, 60
Extraction, II, 49; III, 88
Fehling's solution, I, 26
Ferrous sulfate, II, 79
Ferrous sulfide, III, 12
Formaldehyde, II, 17; 111,67; IV, 47,
53
Formic acid, I, 15 18
Friedel and Crafts' Reaction, IV, 73, 81
Furfural, I, 49-52
G
Gelatine, II, 37
Glycerol, I, 15, 17; II, 29, 33, 79
Glycerol , 7-dichlorohydrin, II, 29-31,
III, 47
Glycerol a-monochlorohydrin, II, 33-35
Glycine, IV, 31-33
Grignard Reaction, IV, 59
Guaiacol, III, 28
H
Hydrazine sulfate, II, 37-40
Hydrobromic acid, I, i, 2-3, 4-11, 36,
39; III, 25, 28, 43; IV, 31
a-Hydroformaminc cyanide, IV, 47
Hydrogen peroxide, III, 27
Hydrogen sulfide, III, u
Hydrolysis, II, 27, 59, 63; III, 25, 53;
IV, 31, 77
Hydroquinone, II, 85
Hydroxyhydroquinone triacetate, IV,
35-36, 45
Hydroxylamine hydrochloride, III, 61-
64
I
Imide formation, II, 75
lodination, IV, 37
Iodine, I, 53, 54; III, 45; IV, 37
lodoform, I, 57, 58
0-Iodophenol, IV, 37-38
K
Ketene, IV, 39-42
Lauryl alcohol, I, 7
Lauryl bromide, I, 7
M
Magnesium, IV, 59
Malonic ester synthesis, IV, n, 29
Mandelic acid, IV, i
Mercuration, III, 65, 99; IV, 13
Mercuric acetate, IV, 13
Mercuric chloride, III, 99
Mercuric iodide, IV, 37
Mercuric sulfate, IV, 23
Mercurous chloride, HI, 100
Mercury di-/>-tolyl, III, 65-66
Mesitylene, II, 41-45
Mesityl oxide, I, 53~55
Methylal, III, 67, 69
Methyl alcohol, III, 29, 71; IV, 3, 16,
3i
Methylamine hydrochloride, I, 81; III,
67-70
0-Methyl anthraquinone, IV, 43-44
Methyl benzoate, III, 71, 72
Methyl bromide, III, 29
Methylene aminoacetonitrile, IV, 31,
47-48
Methylene iodide, I, 57-59
^-Methyl esculetin, IV, 45-46
Methyl formate, III, 67
Methyl hexyl carbinol, I, 61-66
Methyl iodide, I, 57, 59
Methyl o-nitrobenzoate, III, 72
88
INDEX
Methyl w-nitrobenzoate, III, 71-72, 73
Methyl Red, II, 47-61
N
Naphthalene, I, 35, 36
a-Naphthol, III, 7, 9
/3-Naphthoi, II, 6 1
Nicotine, IV, 49
Nicotinic acid, IV, 49-51
Nitration, II, 57; III, 71
Nitric acid, I, 25, 26; II, 57; III, 71;
IV, 27, 49
3-Nitro-4-aminotoluene, III, 91
;-Nitroaniline, III, 79, 87
Nitrobenzene, II, 79; IV, 19, 57
;w-Nitrobenzoic acid, III, 73-74
/>-Nitrobenzoic acid, II, 53-55; III, 75,
76
/>-Nitrobenzoyl chloride, III, 75-77
/>-Nitrobenzyl cyanide, II, 57-58, 59
w-Nitrochlorobenzene, III, 79-81
Nitromethane, III, 83-85
w-Nitrophenol, III, 87
^-Nitrophenylacetic acid, II, 69-60, III,
ii
Nitrosation, II, 17, 61; IV, 19
/>-Nitrosodimethylanilinehydrochloride,
II,i7
Nitroso-/3-naphthol 7 II, 61-62
Nitroso-/3-phenylhydroxylamine, IV, 21
w-Nitrotoluene, III, 91-93
/>-Nitrotoluene, II, 53
w-Nitro-^-toluidine, III, 91
Nitrous anhydride, IV, 27
O
w-Octyl alcohol, I, 7
w-Octyl bromide, I, 7
Oxalic acid, I, 17, 18; II, 23
Oxalic acid ^anhydrous), I, 18, 67-70
Paraformaldehyde, I, 75, 79, 81
Pentaerythritol, IV, 53-56
Phenol, II, 39; IV, 13, 65
Phenol burns, IV, 14
Phenolphthalein, III, 83
Phenolsulfonic acid, III, 51
Phenylacetic acid, II, 10, 63-6$
Phenylacetylene, II, 67-69
Phenylhydrazine, II, 71-74
0-Phenylhydroxylamine, IV, 19, 67-68
Phenylurea, III, 95-97
Phosphoric acid, III, 21
Phosphorus, III, 45
Phosphorus oxychloride, I, 22; III, 75
Phosphorus pentachloride, I, 21, 22;
HI, 75, 76
Phosphorus trichloride, IV, 9
Phthalic anhydride, II, 75; IV, 43, 73
Phthalimide, II, 75-77
Picric acid, IV, 16
Potassium acid sulfate, IV, 63
Potassium hydroxide, I, 29; II, 67; III,
37
Potassium iodide, IV, 37
w-Propylbenzene, IV, 69-61
Propylene bromide, I, 3, 11
Pyridine, IV, 31
Pyrogenic decomposition, IV, 39
Pyruvic acid, IV, 63-64
Quinoline, II, 79-83
Quinone, II, 86-88
Salicylaldehyde, III, 27
Salting-out, IV, 57
Saponification, III, 73
Sodium acetate, II, 48
Sodium alcoholate, IV, 11
Sodium arsenite, I, 57, 58; IV, 5
Sodium arsonoacetate, IV, 6
Sodium benzenesulfonate, I, 21, 22
Sodium benzylate, II, 6
Sodium bisulfite, I, 62, 63; III, 33, 45,
61, 79
Sodium bromide, I, 2, 6, 8, 10
Sodium chloride, IV, 13
Sodium cyanide, I, 33; II, 9; III, 53,
57; IV, 47, 69
Sodium dichromate, II, 13, 53, 85, 95
Sodium formate, III, 69
Sodium hydrosulfite, III, 8, 10
INDEX
89
Sodium ^-hydroxyphenylarsonate, IV,
65-68
Sodium hypophosphite, IV, 6
Sodium iodide, III, 65
Sodium, metallic, II, 5, 42; IV, n, 29
Sodium nitrite, II, 17, 47, 61, 71, 80;
111,7,33,61,79,83,87,91; IV, 69
Sodium sulfite, II, 71; III, 33
Sodium ^-toluenesulfinate, II, 89-91;
III, 99
Sodium />-toluenesulfonate, III, 37, 38
Sulfosalicylic acid, III, 51
Sulfur dioxide, II, 71; III, 9, 61
Sulfuric acid, fuming, IV, 43
Tartaric acid, I, 46; IV, 63
Tetrabromophenolsulfonphthalein, III,
14
Tetra-hydroxymethylmethane, IV, 53-
56
Thionyl chloride, IV, i
Thiophenol, I, 71-74
Toluene, II, 48; III, 27, 30, 42; IV,
23, 73
/>-Toluenesulfonyl chloride, II, 89
0-Toluidine, irt, 33; IV, 69
^-Toluidine, III, 34; IV, 70
o-Tolunitrile, IV, 69-72
/>-Tolunitrile, IV, 69-72
/>-Tolyl-0-benzoic acid, IV, 43, 73-75
/>-Tolylmercuric chloride, III, 85, 99-
100
Tricarballylic acid, IV, 77-79
Trimethylamine, I, 75-78
Trimethylamine hydrochloride, I, 75,
79-82
Trimethylene bromide, I, 2, 8, 10, n
Trimethylene bromohydrin, I, n
Trimethylene glycol, I, 8
1, 3, 5-Trinitrobenzene, II, 93-94, 96
2, 4, 6-Trinitrobenzoic acid, IT, 93, 95-
97
2, 4, 6-Trinitrotoluene, II, 93, 95
Triphenylmethane, IV, 81-83
U
Urea, III, 95
X
Xylene, III, 65, 99
Zinc chloride, IV, 15
Zinc dust, I, 71, 72; II, 89, IV, 57